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Theileria orientalis (Ikeda) was first detected in New Zealand in 2012, becoming endemic in most of the North Island, and can cause incidences of anaemia and death. Research has been performed in New Zealand on the incidence and severity of infection. Through this research anecdotal evidence has been found to suggest a potential genetic susceptibility component in the response of the host to the parasite. To investigate the genetic susceptibility of cattle to T. orientalis (Ikeda), 99 calves born in 2016 as part of a separate experiment and grown in six grazing herds, were examined for their response to the parasite. In addition to measuring live weight, two blood collections were taken in the first four months of life which were used to measure packed cell volume by haematocrit and qPCR to assess parasite load. Heritability was calculated and was low for parasite load, but the result indicates that there is some potential to increase resistance through selective breeding. The mechanisms of the differences in parasite load were not elucidated in this research; however, significant variation was found among herds and sires, indicating that both genetic selection and environmental management could be utilised to reduce parasite load in growing calves. [ABSTRACT FROM AUTHOR]

Simple Summary: Spontaneous humeral fractures in first- and second-lactation dairy cows are recognized as a serious welfare problem in New Zealand. However, the condition is sporadic, which means that simple epidemiological descriptions and estimates of the extent of the problem are lacking. By combining the data from four independent studies using a multi-method approach, we found that their occurrence is more common than previously thought, with potentially up to 12% of farms and 4,620 dairy cattle affected in the 2013/2014 lactation season. Furthermore, the condition exclusively affects first- and second-lactation spring calving dairy cows, up to 4 months post-partum, and may affect multiple animals on the same farm, in the same season, and over multiple seasons, which are not always consecutive. We suggest that the evidence presented in this paper places an urgent requirement on the New Zealand dairy industry to undertake prompt action to understand the determinants of this epidemic. A multi-method approach integrating data from four independent sources was used to describe some key features of the epidemiology and estimate the herd and within-herd incidence of fractured humeri in New Zealand dairy cattle for the period 2007–2015. The first dataset was from a national case series where cases of humeral fractures in dairy cattle were identified by veterinarians across New Zealand between the 2007/2008 and 2011/2012 lactation seasons. The second dataset was from a pet food company based in the Waikato region, which collated the number of casualty first- and second-lactation cows found to have a fractured humerus post-slaughter in the 2014/2015 lactation season, and the third dataset was a case series conducted by veterinarians employed in a Waikato veterinary business, also from the 2014/2015 lactation season. For the final dataset, 505 randomly selected New Zealand dairy farmers completed a phone survey on the incidence of non-responsive, non-weight-bearing forelimb lameness in first- and second-lactation cows in the 2014/2015 lactation season. Using the telephone survey results, the within-herd and herd-level incidence of cases for first- and second-lactation dairy animals was calculated. The national case series reported 149 cases of humeral fractures in 22 dairy herds; the pet food case series identified 61 cases from 41 farms; and the practice-based case series found 14 cases from 10 farms. Humeral fractures exclusively affected first- and second-lactation dairy cows and had a peak incidence between calving and early mating. The national telephone survey found that non-weight-bearing forelimb lameness requiring euthanasia of first- or second-lactation cows occurred in 11.7% of herds, with a mean within-herd incidence of 2.6% for first lactation cows and 2.8% for second-lactation cows for affected herds. These combined datasets demonstrate that humeral fractures in young, lactating dairy cattle are more common than previously suspected and that they occur nationally and over multiple years on some farms. Further work on this condition is urgently required in New Zealand to establish cost-effective management practices that will reduce unnecessary animal suffering and waste. [ABSTRACT FROM AUTHOR]

Outbreaks of humeral fractures in dairy cows have been reported in New Zealand for several years. Gross, histologic, and histomorphometric findings in the humerus from primiparous cows with spontaneous humeral fracture were compared to age-matched control cows. Affected cows had a complete nonarticular spiral fracture of the humerus. Histologically affected humeri had a thicker growth plate with abnormal architecture, thinner cortex with increased abnormal resorption, increased resorption in the distal humerus, decreased trabecular density, abnormal trabecular architecture, presence of growth arrest lines and woven bone formation. Histomorphometry showed reduction in bone volume, trabecular perimeter, and trabecular width. Cows grazed on fodder beet had thicker growth plates with an abnormal appearance compared with cows grazed on pasture, and cows with low/marginal liver copper concentration had more resorption cavities in the distal humerus and thinner cortical bone compared with cows with adequate liver copper concentration. Decreased trabecular density (OR = 249.5), abnormal cortical resorption (OR = 54.2), presence of woven bone formation in the proximal metaphysis (OR = 37.2), and the number of resorption cavities in the distal humerus were significantly associated with a high probability of fracture. Ribs had enlargement of the costochondral junction with fractures in different stages of healing. Histology of the ribs revealed abnormal growth plate appearance, presence of fracture lines, callus tissue, fibrosis, and microfractures. Cows with humeral fracture have osteoporosis due to decreased bone formation and increased bone resorption, likely associated with inadequate feed quality and perhaps copper deficiency leading to a reduction in bone strength and fracture. [ABSTRACT FROM AUTHOR]

Herein, we assessed the utility of the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS) to predict burn-specific outcomes. We hypothesized that frail patients are at greater risk for burn-related complications and require increased healthcare support at discharge. Patients 50 years and older admitted to our institution for burn injuries between July 2009 and June 2019 were included. Demographics, comorbidities, pre-injury functional status, injury and hospitalization information, complications (graft loss, acute respiratory failure, and acute kidney disease [AKI]), mortality, and discharge disposition were collected. Multivariate analyses were performed to assess the association between admission frailty scored using the CSHA-CFS and outcomes. P <.05 was considered significant. Eight-hundred fifty-one patients were included, 697 were not frail and 154 were frail. Controlling for Baux scores, sex, race, mechanism of injury, 2nd and 3rd degree burn surface, and inhalation injury, frailty was associated with acute respiratory failure (OR = 2.599 [1.460–4.628], P =.001) and with mortality (OR = 6.080 [2.316–15.958]; P <.001). Frailty was also associated with discharge to skilled nursing facility, rehabilitation, or long-term acute care facilities (OR = 3.135 [1.784–5.508], P <.001), and to hospice (OR = 8.694 [1.646–45.938], P =.011) when compared to home without healthcare services. Frailty is associated with increased risk of acute respiratory failure, mortality, and requiring increased healthcare support post-discharge. Our data suggest that frailty can be used as a tool to predict morbidity and mortality and for goals of care discussions for the burn patient. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne bandavirus mainly transmitted by Haemaphysalis longicornis ticks in East Asia, mostly in rural areas. As of April 2022, the amplifying host involved in the natural transmission of SFTSV remained unidentified. Our epidemiologic field survey conducted in endemic areas in China showed that hedgehogs were widely distributed, had heavy tick infestations, and had high SFTSV seroprevalence and RNA prevalence. After experimental infection of Erinaceus amurensis and Atelerix albiventris hedgehogs with SFTSV, we detected robust but transitory viremias that lasted for 9-11 days. We completed the SFTSV transmission cycle between hedgehogs and nymph and adult H. longicornis ticks under laboratory conditions with 100% efficiency. Furthermore, naive H. longicornis ticks could be infected by SFTSV-positive ticks co-feeding on naive hedgehogs; we confirmed transstadial transmission of SFTSV. Our study suggests that the hedgehogs are a notable wildlife amplifying host of SFTSV in China. [ABSTRACT FROM AUTHOR]

Aim: Species distribution models typically project climatically suitable habitat for trees in eastern North America to shift hundreds of kilometres this century. We simulated potential migration, accounting for various traits that affect species' ability to track climatically suitable habitat. Location: Eastern Canada, covering ~3.7 million km2. Methods: We simulated migration‐constrained range shifts through 2100 using a hybrid approach combining projections of climatically suitable habitat based on two Representative Concentration Pathways (RCP4.5, RCP8.5) for three time periods and two species distribution modelling approaches with process‐based models parameterized using data related to dispersal ability and generation time. We developed a unique "migration kernel" that uses seed dispersal traits and observed migration velocities to obtain kernel shape and dispersal probabilities for each tree species. We then calculated lags between the migration‐constrained range limits obtained through simulations and limits of climatically suitable habitat. Results: All species demonstrated northward range shifts at the leading edge of their simulated distribution through 2100, but the magnitude and rate of that shift varied by species and time period. Climatically suitable habitat limits were found to be north of simulated distribution limits across both RCPs, with lags increasing through time. On average, simulated distribution that remained within climatically suitable habitat declined more under RCP8.5 than RCP4.5, with large areas of the rear edge of the simulated distribution becoming partially or completely climatically unsuitable for many species. Main conclusions: Climatically suitable habitat limits projected for 2100 far exceeded migration‐constrained range limits for all 10 tree species, particularly for temperate species. This study underlines the limited extent to which tree species will track climate change via natural migration. Integrating observed migration velocities, seed dispersal and generation time with SDM outputs allows for more realistic evaluations of tree migration ability under climate change and may help orient forest conservation and restoration efforts. [ABSTRACT FROM AUTHOR]

Simple Summary: Collagen and collagen crosslinking are important determinants of bone strength. For the first time, collagen and its crosslink content were measured in the humerus from primiparous dairy cows with spontaneous humeral fracture due to osteoporosis from New Zealand. The results were compared with the humerus from unfractured dairy cows. Cows with a humeral fracture have a lower total collagen content but higher total collagen crosslink content compared with unfractured cows. The results suggest that protein/calorie undernutrition might be an important factor associated with the incidence of spontaneous humeral fractures in dairy cows from New Zealand. Numerous cases of spontaneous humeral fracture in primiparous dairy cows from New Zealand have prompted the study of the condition to establish probable causes or risk factors associated with the condition. Previous studies identified inadequate protein-calorie malnutrition as an important contributory factor. Earlier case studies also reported that ~50% of cows have low liver and/or serum copper concentration at the time of humeral fracture. Because copper is so closely associated with the formation of collagen cross-links, the aim of this study was to compare collagen and collagen crosslink content in the humerus from primiparous cows with and without humeral fractures and to determine the role of copper in the occurrence of these fractures. Humeri were collected from cows with and without humeral fractures, ground, and the collagen and collagen cross-link content measured using high-performance liquid chromatography. Collagen content was significantly higher in the humeri of cows without humeral fractures, while total collagen crosslink content was significantly higher in the humerus of cows with humeral fractures. These results indicate other factor/s (e.g., protein-calorie undernutrition) might be more important than the copper status in the occurrence of humeral fractures in dairy cows in New Zealand. [ABSTRACT FROM AUTHOR]

Post-traumatic OA (PTOA) is often triggered by injurious, high-impact loading events which result in rapid, excessive chondrocyte cell death and a phenotypic shift in residual cells toward a more catabolic state. As such, the identification of a disease-modifying OA drug (DMOAD) that can protect chondrocytes from death following impact injury, and thereby prevent cartilage degradation and progression to PTOA, would offer a novel intervention. We have previously shown that urocortin-1 (Ucn) is an essential endogenous pro-survival factor that protects chondrocytes from OA-associated pro-apoptotic stimuli. Here, using a drop tower PTOA-induction model, we demonstrate the extent of Ucn's chondroprotective role in cartilage explants exposed to excessive impact load. Using pathway-specific agonists and antagonists, we show that Ucn acts to block load-induced intracellular calcium accumulation through blockade of the non-selective cation channel Piezo1 rather than TRPV4. This protective effect is mediated primarily through the Ucn receptor CRF-R1 rather than CRF-R2. Crucially, we demonstrate that the chondroprotective effect of Ucn is maintained whether it is applied pre-impact or post-impact, highlighting the potential of Ucn as a novel DMOAD for the prevention of injurious impact overload-induced PTOA. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is spreading rapidly in Asia. This virus is transmitted by the Asian longhorned tick (Haemaphysalis longicornis), which has parthenogenetically and sexually reproducing populations. Parthenogenetic populations were found in ≥15 provinces in China and strongly correlated with the distribution of severe fever with thrombocytopenia syndrome cases. However, distribution of these cases was poorly correlated with the distribution of populations of bisexual ticks. Phylogeographic analysis suggested that the parthenogenetic population spread much faster than bisexual population because colonization is independent of sexual reproduction. A higher proportion of parthenogenetic ticks was collected from migratory birds captured at an SFTSV-endemic area, implicating the contribution to the long-range movement of these ticks in China. The SFTSV susceptibility of parthenogenetic females was similar to that of bisexual females under laboratory conditions. These results suggest that parthenogenetic Asian longhorned ticks, probably transported by migratory birds, play a major role in the rapid spread of SFTSV. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether the infection intensity of Theileria orientalis Ikeda type organisms within Haemaphysalis longicornis larvae and nymph stages fluctuated over 6 mo after feeding as larvae on infected calves in the field. Naı¨ve larvae, hatched from eggs, were fed on infected calves for 5 days while contained within cotton socks glued over the calves’ ears. Larvae were first sampled immediately post-feeding and then sampled every 3 wk for 23 wk in total, after molting to nymphs. All larvae and nymphs were tested for T. orientalis Ikeda organisms using quantitative PCR. The qPCR results showed that the infection intensity of Haemaphysalis longicornis larvae and nymphs was not constant over the sampling period, and after initially dropping after molting to nymphs, it then rose with fasting to a maximum at 17 and 23 wk post-feeding. The significant rise in T. orientalis Ikeda organisms observed at 23 wk postfeeding may explain why more severe clinical cases of bovine theileriosis in New Zealand are seen in the spring when nymphs are the predominant instar questing. [ABSTRACT FROM AUTHOR]

This study presents spatial models (i.e., thin-plate spatially continuous spline surfaces) of adjusted precipitation for Canada at daily, pentad (5 day), and monthly time scales from 1900 to 2015. The input data include manual observations from 3346 stations that were adjusted previously to correct for snow water equivalent (SWE) conversion and various gauge-related issues. In addition to the 42 331 models for daily total precipitation and 1392 monthly total precipitation models, 8395 pentad models were developed for the first time, depicting mean precipitation for 73 pentads annually. For much of Canada, mapped precipitation values from this study were higher than those from the corresponding unadjusted models (i.e., models fitted to the unadjusted data), reflecting predominantly the effects of the adjustments to the input data. Error estimates compared favorably to the corresponding unadjusted models. For example, root generalized cross-validation (GCV) estimate (a measure of predictive error) at the daily time scale was 3.6 mm on average for the 1960–2003 period as compared with 3.7 mm for the unadjusted models over the same period. There was a dry bias in the predictions relative to recorded values of between 1% and 6.7% of the average precipitations amounts for all time scales. Mean absolute predictive errors of the daily, pentad, and monthly models were 2.5 mm (52.7%), 0.9 mm (37.4%), and 11.2 mm (19.3%), respectively. In general, the model skill was closely tied to the density of the station network. The current adjusted models are available in grid form at ~2–10-km resolutions. [ABSTRACT FROM AUTHOR]

International classification of disease (ICD) codes can improve the efficiency of epidemiological research provided the codes accurately identify outcomes of interest. The purpose of this retrospective cross-sectional study is to evaluate the accuracy of ICD-10 codes for identifying thromboembolic events occurring during anticoagulation therapy. Medical charts of patients hospitalized for any reason while receiving anticoagulant therapy between September 1, 2017 and December 31, 2017 were reviewed by two reviewers blinded to ICD-10 code status. Following identification of confirmed acute thromboembolic events, ICD-10 codes were unblinded and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) along with 95% confidence intervals (CI) were calculated for coding in any diagnosis position ("principal" or "other"). There were 661 hospitalizations identified among 487 anticoagulated patients. There were 27 thromboembolic events identified during chart review. Stroke and venous thromboembolism were the most common thromboembolic event types. Overall thromboembolic ICD-10 coding sensitivity was 100.0% (95% CI 87.2–100.0); specificity was 79.3% (75.9–82.4). PPV was 17.1% (11.6–23.9%), and NPV was 100% (99.3–100.0). ICD-10 codes can reliably be used for ruling out hospitalizations for thromboembolic events in patients receiving anticoagulation therapy but should not be used for identifying thromboembolic complications without confirmatory chart review. [ABSTRACT FROM AUTHOR]

The post-translational modification of proteins has been shown to be extremely important in prokaryotes. Using a highly sensitive mass spectrometry-based proteomics approach, we have characterized the acetylome of B. burgdorferi. As previously reported for other bacteria, a relatively low number (5%) of the potential genome-encoded proteins of B. burgdorferi were acetylated. Of these, the vast majority were involved in central metabolism and cellular information processing (transcription, translation, etc.). Interestingly, these critical cell functions were targeted during both ML (mid-log) and S (stationary) phases of growth. However, acetylation of target proteins in ML phase was limited to single lysine residues while these same proteins were acetylated at multiple sites during S phase. To determine the acetyl donor in B. burgdorferi , we used mutants that targeted the sole acetate metabolic/anabolic pathway in B. burgdorferi (lipid I synthesis). B. burgdorferi strains B31-A3, B31-A3 Δ ackA (acetyl-P- and acetyl-CoA-) and B31-A3 Δ pta (acetyl-P+ and acetyl-CoA-) were grown to S phase and the acetylation profiles were analyzed. While only two proteins were acetylated in the Δ ackA mutant, 140 proteins were acetylated in the Δ pta mutant suggesting that acetyl-P was the primary acetyl donor in B. burgdorferi. Using specific enzymatic assays, we were able to demonstrate that hyperacetylation of proteins in S phase appeared to play a role in decreasing the enzymatic activity of at least two glycolytic proteins. Currently, we hypothesize that acetylation is used to modulate enzyme activities during different stages of growth. This strategy would allow the bacteria to post-translationally stimulate the activity of key glycolytic enzymes by deacetylation rather than expending excessive energy synthesizing new proteins. This would be an appealing, low-energy strategy for a bacterium with limited metabolic capabilities. Future work focuses on identifying potential protein deacetylase(s) to complete our understanding of this important biological process. [ABSTRACT FROM AUTHOR]

In recent years, the number of Lyme disease or borreliosis cases in Eurasia has been dramatically increasing. This tick-borne disease is caused by Borrelia burgdorferi sensu lato, which includes B. burgdorferi sensu stricto, the main species found in North America, and B. afzelii and B. garinii, which are primarily responsible for the disease in Eurasia. Currently, research on Lyme disease has focused mainly on B. burgdorferi while B. afzelii and B. garinii, which cause disease with distinctly different symptoms, are less studied. The purpose of this study is to evaluate B. afzelii BO23 and B. garinii CIP 103362 as model organisms to study Eurasian Lyme disease. To begin our analyses, we sequenced, annotated the chromosomes of both species and compared them to B. burgdorferi strain B31. We also assayed shuttle vector, pBSV2, for transformation efficacy and demonstrated that these strains can be cultured on solid media. In addition, we characterized how physicochemical parameters (e.g., oxygen, osmolarity, oxidative stress) affect both growth and motility of the bacteria. Finally, we describe each strain’s antibiotic susceptibility and accessed their ability to infect mice. In conclusion, B. afzelii BO23 was more practical for in vitro and in vivo studies than B. garinii CIP 103362. [ABSTRACT FROM AUTHOR]

Summary: Polyamines are an essential class of metabolites found throughout all kingdoms in life. Borrelia burgdorferi harbors no enzymes to synthesize or degrade polyamines yet does contain a polyamine uptake system, potABCD. In this report, we describe the initial characterization of this putative transport system. After several unsuccessful attempts to inactivate potABCD, we placed the operon under the control of an inducible LacI promoter expression system. Analyses of this construct confirmed that potABCD was required for in vitro survival. Additionally, we demonstrated that the potABCD operon were upregulated in vitro by low osmolarity. Previously, we had shown that low osmolarity triggers the activation of the Rrp2/RpoN/RpoS regulatory cascade, which regulates genes essential for the transmission of spirochetes from ticks to mammalian hosts. Interestingly, induction of the pot operon was only affected in an rpoS mutant but not in a rpoN mutant, suggesting that the genes were RpoS dependent and RpoN independent. Furthermore, potABCD was upregulated during tick feeding concomitant with the initiation of spirochete replication. Finally, uptake experiments determined the specificity of B. burgdorferi's PotABCD for spermidine. [ABSTRACT FROM AUTHOR]

The spirochete Borrelia burgdorferi survives in its tick vector, Ixodes scapularis, or within various hosts. To transition between and survive in these distinct niches, B. burgdorferi changes its gene expression in response to environmental cues, both biochemical and physiological. Exposure of B. burgdorferi to weak monocarboxylic organic acids, including those detected in the blood meal of fed ticks, decreased the cytoplasmic pH of B. burgdorferi in vitro. A decrease in the cytoplasmic pH induced the expression of genes encoding enzymes that have been shown to restore pH homeostasis in other bacteria. These include putative coupled proton/cation exchangers, a putative Na+/H+ antiporter, a neutralizing buffer transporter, an amino acid deaminase and a proton exporting vacuolar-type VoV1 ATPase. Data presented in this report suggested that the acid stress response triggered the expression of RpoN- and RpoS-dependent genes including important virulence factors such as outer surface protein C (OspC), BBA66, and some BosR (Borrelia oxidative stress regulator)-dependent genes. Because the expression of virulence factors, like OspC, are so tightly connected by RpoS to general cellular stress responses and cell physiology, it is difficult to separate transmission-promoting conditions in what is clearly a multifactorial and complex regulatory web. [ABSTRACT FROM AUTHOR]

Urocortin ( UCN1) peptide shares structural and functional homology with corticotropin-releasing factor ( CRF). UCN1 is significantly reduced in endometrial adenocarcinoma compared to healthy controls. However, there are no data which evaluate the effects of UCN1 in the endometrium, or how it is modulated. We used proliferation and transwell assays to determine the effect of UCN1 on the proliferation and migration of Ishikawa and HEC1A cells. We also determined the expression levels of UCN1 and its receptors produced by estrogen receptor agonists, and the effect of UCN1 on estrogen receptor expression, using quantitative polymerase chain reaction. UCN1 suppressed migration of endometrial cancer cells in vitro. This effect appears to be specific to CRF receptor 2 ( CRFR2), as selective antagonism of CRFR2 but not CRFR1 completely eliminated suppression of migration. Activation of ERA reduced UCN1 expression, but only had a small effect on the expression of CRFR1. However, expression of CRFR2 was more notably reduced at both the m RNA and protein levels by activation of ERB. UCN1 in turn reduced both ERA and ERB expression, as assessed by real-time quantitative PCR. We demonstrate that UCN1 significantly suppresses the migration of endometrial cancer cells but has no effect on their proliferation. Thus, loss of UCN1 in endometrial cancer may promote invasion and metastatic spread. There is a complex relationship between the UCN1 system and estrogen receptors, which may provide insights into endometrial carcinogenesis, a disease known to be driven by estrogen excess. [ABSTRACT FROM AUTHOR]

The Lyme disease spirochete Borrelia burgdorferi encounters a wide range of environmental conditions as it cycles between ticks of the genus Ixodes and its various mammalian hosts. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are potent antimicrobial molecules generated during the innate immune response to infection, however, it is unclear whether ROS and RNS pose a significant challenge to B. burgdorferi in vivo. In this study, we screened a library of B. burgdorferi strains with mutations in DNA repair genes for increased susceptibility to ROS or RNS in vitro. Strains with mutations in the methyl-directed mismatch repair gene mutS1 are hypersensitive to killing by ROS, while strains lacking the nucleotide excision repair (NER) gene uvrB show increased susceptibility to both ROS and RNS. Therefore, mutS1 deficient and uvrBdeficient strains were compared for their ability to complete their infectious cycle in Swiss Webster mice and I. scapularis ticks to help identify sites of oxidative and nitrosative stresses encountered by B. burgdorferi in vivo. Both mutS1 and uvrB were dispensable for infection of mice, while uvrB promoted the survival of spirochetes in I. scapularis ticks. The decreased survival of uvrB-deficient B. burgdorferi was associated with the generation of RNS in I. scapularis midguts and salivary glands during feeding. Collectively, these data suggest that B. burgdorferi must withstand cytotoxic levels of RNS produced during infection of I. scapularis ticks. [ABSTRACT FROM AUTHOR]

Lyme disease, caused by Borrelia burgdorferi, is a vector-borne illness that requires the bacteria to adapt to distinctly different environments in its tick vector and various mammalian hosts. Effective colonization (acquisition phase) of a tick requires the bacteria to adapt to tick midgut physiology. Successful transmission (transmission phase) to a mammal requires the bacteria to sense and respond to the midgut environmental cues and up-regulate key virulence factors before transmission to a new host. Data presented here suggest that one environmental signal that appears to affect both phases of the infective cycle is osmolarity. While constant in the blood, interstitial fluid and tissue of a mammalian host (300 mOsm), osmolarity fluctuates in the midgut of feeding Ixodes scapularis. Measured osmolarity of the blood meal isolated from the midgut of a feeding tick fluctuates from an initial osmolarity of 600 mOsm to blood-like osmolarity of 300 mOsm. After feeding, the midgut osmolarity rebounded to 600 mOsm. Remarkably, these changes affect the two independent regulatory networks that promote acquisition (Hk1-Rrp1) and transmission (Rrp2-RpoN-RpoS) of B. burgdorferi. Increased osmolarity affected morphology and motility of wild-type strains, and lysed Hk1 and Rrp1 mutant strains. At low osmolarity, Borrelia cells express increased levels of RpoN-RpoS-dependent virulence factors (OspC, DbpA) required for the mammalian infection. Our results strongly suggest that osmolarity is an important part of the recognized signals that allow the bacteria to adjust gene expression during the acquisition and transmission phases of the infective cycle of B. burgdorferi. [ABSTRACT FROM AUTHOR]

In B. burgdorferi, the Rrp2-RpoN-RpoS signaling cascade is a distinctive system that coordinates the expression of virulence factors required for successful transition between its arthropod vector and mammalian hosts. Rrp2 (BB0763), an RpoN specific response regulator, is essential to activate this regulatory pathway. Previous investigations have attempted to identify the phosphate donor of Rrp2, including the cognate histidine kinase, Hk2 (BB0764), non-cognate histidine kinases such as Hk1, CheA1, and CheA2, and small molecular weight P-donors such as carbamoyl-phosphate and acetyl-phosphate (AcP). In a report by Xu et al., exogenous sodium acetate led to increased expression of RpoS and OspC and it was hypothesized this effect was due to increased levels of AcP via the enzyme AckA (BB0622). Genome analyses identified only one pathway that could generate AcP in B. burgdorferi: the acetate/mevalonate pathway that synthesizes the lipid, undecaprenyl phosphate (C55-P, lipid I), which is essential for cell wall biogenesis. To assess the role of AcP in Rrp2–dependent regulation of RpoS and OspC, we used a unique selection strategy to generate mutants that lacked ackA (bb0622: acetate to AcP) or pta (bb0589: AcP to acetyl-CoA). These mutants have an absolute requirement for mevalonate and demonstrate that ackA and pta are required for cell viability. When the ΔackA or Δpta mutant was exposed to conditions (i.e., increased temperature or cell density) that up-regulate the expression of RpoS and OspC, normal induction of those proteins was observed. In addition, adding 20mM acetate or 20mM benzoate to the growth media of B. burgdorferi strain B31 ΔackA induced the expression of RpoS and OspC. These data suggest that AcP (generated by AckA) is not directly involved in modulating the Rrp2-RpoN-RpoS regulatory pathway and that exogenous acetate or benzoate are triggering an acid stress response in B. burgdorferi. [ABSTRACT FROM AUTHOR]

This study produced annual spatial models (or grids) of 27 growing-season variables for Canada that span two centuries (1901-2100). Temporal gaps in the availability of daily climate data-the typical and preferred source for calculating growing-season variables-necessitated the use of two approaches for generating these growing-season grids. The first approach, used only for the 1950-2010 period, employed a computer script to directly calculate the suite of growing-season variables from existing daily climate grids. Since daily grids were not available for the remaining years, a second approach, which employed a machine-learning method called boosted regression trees (BRT), was used to generate statistical models that related each growing-season variable to a suite of climate and water-related predictors. These BRT models were used to generate grids of growing-season variables for each year of the study period, including the 1950-2010 period to allow comparison between the two approaches. Mean absolute errors associated with the BRT-based grids were approximately 30% higher than those associated with the daily-based grids. The two approaches were also compared by calculating trends in growing-season length over the 1950-2010 period. Significant increases in growing-season length were obtained for nearly all ecozones across Canada, and there were no significant differences in the trends obtained from the two approaches. Although the daily-based approach tended to have lower errors, the BRT approach produced comparable map products that should be valuable for periods and regions for which daily data are not available. [ABSTRACT FROM AUTHOR]

We present 50-year updates for two plant hardiness models (maps), developed originally by Agriculture Canada and the US Department of Agriculture (USDA), that are widely used for plant selection decisions in Canada. The updated maps show clear northward shifts in hardiness zones across western Canada. Shifts are less dramatic in southeastern Canada, with modest increases in zone values associated with the Canadian map but modest declines associated with the USDA approach. Species-specific climate envelope models are an alternative to generalized hardiness zones. We generated climate envelopes for 62 northern tree species over the same 50-year interval and found an average northward shift of 57 kilometers. These changes signal an increase in the productivity and diversity of plants that can be grown in Canada. However, late spring frosts and other factors discussed herein may limit the extent to which this potential is realized. [ABSTRACT FROM AUTHOR]

A precise control of vesicular trafficking is crucial not only for osteoclastic bone resorption, but also for the crosstalk between osteoclasts and osteoblasts, which regulates bone homeostasis. In addition to the release of growth factors and modulators, such as glutamate, flux through the intracellular trafficking routes could also provide the osteoclast with a monitoring function of its resorption activity. To establish the signaling pathways regulating trafficking events in resorbing osteoclasts, we used the bone conserving hormone calcitonin, which has the unique property of inducing osteoclast quiescence. Calcitonin acts through the calcitonin receptor and activates multiple signaling pathways. By monitoring trafficking of a fluorescent low molecular weight probe in mature, bone resorbing osteoclasts we show for the first time that calcitonin blocks endocytosis from the ruffled border by phospholipase C (PLC) activation. Furthermore, we identify a requirement for polyunsaturated fatty acids in endocytic trafficking in osteoclasts. Inhibition of PLC prior to calcitonin treatment restores endocytosis to 75% of untreated rates. This effect is independent of protein kinase C activation and can be mimicked by an increase in intracellular calcium. We thus define an essential role for intracellular calcium levels in the maintenance of endocytosis in osteoclasts. [ABSTRACT FROM AUTHOR]

The article discusses a study on the estimates of the potential cost of emerald ash borer or Agrilus planipennis Faimaire, in Canadian urban areas. The areas were identified through a digital version of Canada's urban areas cartographic boundary file. As an additional focus, probable effects to backyard trees were included. The types of costs that were integrated into the study are removal costs, replacement costs, treatment costs, and community overhead costs.

Over the past two decades, researchers at Natural Resources Canada's Canadian Forest Service, in collaboration with the Australian National University (ANU), Environment Canada (EC), and the National Oceanic and Atmospheric Administration (NOAA), have made a concerted effort to produce spatial climate products (i.e., spatial models and grids) covering both Canada and the United States for a wide variety of climate variables and time steps (from monthly to daily), and across a range of spatial resolutions. Here we outline the method used to generate the spatial models, detail the array of products available and how they may be accessed, briefly describe some of the usage and impact of the models, and discuss anticipated further developments. Our initial motivation in developing these models was to support forestry-related applications. They have since been utilized by a wider range of agencies and researchers. This article is intended to further raise awareness of the strengths and weaknesses of these climate models and to facilitate their wider application. [ABSTRACT FROM AUTHOR]

Summary Borrelia burgdorferi encounters potentially harmful reactive nitrogen species (RNS) throughout its infective cycle. In this study, diethylamine NONOate (DEA/NO) was used to characterize the lethal effects of RNS on B. burgdorferi. RNS produce a variety of DNA lesions in a broad spectrum of microbial pathogens; however, levels of the DNA deamination product, deoxyinosine, and the numbers of apurinic/apyrimidinic (AP) sites were identical in DNA isolated from untreated and DEA/NO-treated B. burgdorferi cells. Strains with mutations in the nucleotide excision repair (NER) pathway genes uvrC or uvrB treated with DEA/NO had significantly higher spontaneous mutation frequencies, increased numbers of AP sites in DNA and reduced survival compared with wild-type controls. Polyunsaturated fatty acids in B. burgdorferi cell membranes, which are susceptible to peroxidation by reactive oxygen species (ROS), were not sensitive to RNS-mediated lipid peroxidation. However, treatment of B. burgdorferi cells with DEA/NO resulted in nitrosative damage to several proteins, including the zinc-dependent glycolytic enzyme fructose-1,6-bisphosphate aldolase (BB0445), the B orrelia oxidative stress regulator (BosR) and neutrophil-activating protein (NapA). Collectively, these data suggested that nitrosative damage to proteins harbouring free or zinc-bound cysteine thiols, rather than DNA or membrane lipids underlies RNS toxicity in wild-type B. burgdorferi. [ABSTRACT FROM AUTHOR]

Yersinia pestis forms a biofilm in the foregut of its flea vector that promotes transmission by flea bite. As in many bacteria, biofilm formation in Y. pestis is controlled by intracellular levels of the bacterial second messenger c-di-GMP. Two Y. pestis diguanylate cyclase (DGC) enzymes, encoded by hmsT and y3730, and one phosphodiesterase (PDE), encoded by hmsP, have been shown to control biofilm production in vitro via their opposing c-di-GMP synthesis and degradation activities, respectively. In this study, we provide further evidence that hmsT, hmsP, and y3730 are the only three genes involved in cdi- GMP metabolism in Y. pestis and evaluated the two DGCs for their comparative roles in biofilm formation in vitro and in the flea vector. As with HmsT, the DGC activity of Y3730 depended on a catalytic GGDEF domain, but the relative contribution of the two enzymes to the biofilm phenotype was influenced strongly by the environmental niche. Deletion of y3730 had a very minor effect on in vitro biofilm formation, but resulted in greatly reduced biofilm formation in the flea. In contrast, the predominant effect of hmsT was on in vitro biofilm formation. DGC activity was also required for the Hmsindependent autoaggregation phenotype of Y. pestis, but was not required for virulence in a mouse model of bubonic plague. Our results confirm that only one PDE (HmsP) and two DGCs (HmsT and Y3730) control c-di-GMP levels in Y. pestis, indicate that hmsT and y3730 are regulated post-transcriptionally to differentially control biofilm formation in vitro and in the flea vector, and identify a second c-di-GMP-regulated phenotype in Y. pestis. [ABSTRACT FROM AUTHOR]

Borrelia burgdorferi is an obligate parasite with a limited genome that severely narrows its metabolic and biosynthetic capabilities. Thus survival of this spirochaete in an arthropod vector and mammalian host requires that it can scavenge amino acids, fatty acids and nucleosides from a blood meal or various host tissues. Additionally, the utilization of ribonucleotides for DNA synthesis is further complicated by the lack of a ribonucleotide reductase for the conversion of nucleoside-5′-diphosphates to deoxynucleosides-5′-diphosphates. The data presented here demonstrate that B. burgdorferi must rely on host-derived sources of purine bases, deoxypurines and deoxypyrimidines for the synthesis of DNA. However, if deoxyguanosine (dGuo) is limited in host tissue, the enzymatic activities of a 2′-deoxyribosyltransferase (DRTase, encoded by bb0426), IMP dehydrogenase (GuaB) and GMP synthase (GuaA) catalyse the multistep conversion of hypoxanthine (Hyp) to dGMP for DNA synthesis. This pathway provides additional biochemical flexibility for B. burgdorferi when it colonizes and infects different host tissues. [ABSTRACT FROM AUTHOR]

The application of trivariate thin-plate smoothing splines to the interpolation of daily weather data is investigated. The method was used to develop spatial models of daily minimum and maximum temperature and daily precipitation for all of Canada, at a spatial resolution of 300 arc s of latitude and longitude, for the period 1961–2003. Each daily model was optimized automatically by minimizing the generalized cross validation. The fitted trivariate splines incorporated a spatially varying dependence on ground elevation and were able to adapt automatically to the large variation in station density over Canada. Extensive quality control measures were performed on the source data. Error estimates for the fitted surfaces based on withheld data across southern Canada were comparable to, or smaller than, errors obtained by daily interpolation studies elsewhere with denser data networks. Mean absolute errors in daily maximum and minimum temperature averaged over all years were 1.1° and 1.6°C, respectively. Daily temperature extremes were also well matched. Daily precipitation is challenging because of short correlation length scales, the preponderance of zeros, and significant error associated with measurement of snow. A two-stage approach was adopted in which precipitation occurrence was estimated and then used in conjunction with a surface of positive precipitation values. Daily precipitation occurrence was correctly predicted 83% of the time. Withheld errors in daily precipitation were small, with mean absolute errors of 2.9 mm, although these were relatively large in percentage terms. However, mean percent absolute errors in seasonal and annual precipitation totals were 14% and 9%, respectively, and seasonal precipitation upper 95th percentiles were attenuated on average by 8%. Precipitation and daily maximum temperatures were most accurately interpolated in the autumn, consistent with the large well-organized synoptic systems that prevail in this season. Daily minimum temperatures were most accurately interpolated in summer. The withheld data tests indicate that the models can be used with confidence across southern Canada in applications that depend on daily temperature and accumulated seasonal and annual precipitation. They should be used with care in applications that depend critically on daily precipitation extremes. [ABSTRACT FROM AUTHOR]

The article reports a case of sweet syndrome or acute febrile neutrophilic dermatoses in a 54-year-old man. A probable etiology of pulmonary infiltrates was sweet syndrome with lung involvement or neutrophilic alveolitis. The patient was treated with systemic corticosteroids and experienced a fast resolution of the rash and pulmonary infiltrates. The patient also underwent a bone marrow biopsy, and the findings were consistent with a myelodysplastic syndrome.

The article cites a study about a 69-year-old morbidly obese woman with a history of ostheoarthritis. The patient has been diagnosed with respiratory failure and thrombocytopenia 15 days after she is presented to a community hospital for a long routine left, total knee arthroplasty. Moreover, she began to make progress in terms of ventilator weaning and on 35 hospital days, she developed mild neutropenia.

Spirochetes living in an oxygen-rich environment or when challenged by host immune cells are exposed to reactive oxygen species (ROS). These species can harm/destroy cysteinyl residues, iron-sulphur clusters, DNA and polyunsaturated lipids, leading to inhibition of growth or cell death. Because Borrelia burgdorferi contains no intracellular iron, DNA is most likely not a major target for ROS via Fenton reaction. In support of this, growth of B. burgdorferi in the presence of 5 mM H2O2 had no effect on the DNA mutation rate (spontaneous coumermycin A1 resistance), and cells treated with 10 mM t-butyl hydroperoxide or 10 mM H2O2 show no increase in DNA damage. Unlike most bacteria, B. burgdorferi incorporates ROS-susceptible polyunsaturated fatty acids from the environment into their membranes. Analysis of lipoxidase-treated B. burgdorferi cells by Electron Microscopy showed significant irregularities indicative of membrane damage. Fatty acid analysis of cells treated with lipoxidase indicated that host-derived linoleic acid had been dramatically reduced (50-fold) in these cells, with a corresponding increase in the levels of malondialdehyde by-product (fourfold). These data suggest that B. burgdorferi membrane lipids are targets for attack by ROS encountered in the various stages of the infective cycle. [ABSTRACT FROM AUTHOR]

Currently predicted change in climate could strongly affect plant distributions during the next century. Here we determine the present-day climatic niches for 130 North American tree species. We then locate the climatic conditions of these niches on maps of predicted future climate, indicating where each species could potentially occur by the end of the century. A major unknown in this work is the extent to which populations of trees will actually track climate shifts through migration. We therefore present two extreme scenarios in which species either move entirely into future climatic niches or do not move out of their current niches. In the full-dispersal scenario, future potential ranges show decreases and increases in size, with an average decrease of 12% and a northward shift of 700 kilometers (km). In the no-dispersal scenario, potential ranges decrease in size by 58% and shift northward by 330 km. Major redistribution pressures appear to be in order under both dispersal scenarios. [ABSTRACT FROM AUTHOR]

Traditional plant hardiness zone maps identify areas that are relatively homogeneous with respect to climatic conditions that affect plant survival. Plants are typically categorized according to the most northerly, and sometimes the most southerly, zone in which they can successfully grow. This approach suffers from a number of limitations, including the coarse spatial nature of the zones and the relatively unsystematic assignment of plants to zones. Here we propose using climate envelopes to map the potential ranges of plant species in North America in wild and cultivated settings. We have initiated a major data-gathering effort that currently includes over 1.8 million georeferenced observations for more than 4100 plant species. We demonstrate the approach using sugar maple (Acer saccharum) and show the ease with which predicted climate-change impacts can be incorporated into the models. [ABSTRACT FROM AUTHOR]

The genome of Borrelia burgdorferi is composed of one linear chromosome and approximately 20 linear and circular plasmids. Although some plasmids are required by B. burgdorferi in vivo, most plasmids are dispensable for growth in vitro. However, circular plasmid (cp) 26 is present in all natural isolates and has never been lost during in vitro growth. This plasmid carries ospC, which is critical for mammalian infection. We previously showed that cp26 encodes essential functions, including the telomere resolvase, ResT, and hence cannot be displaced. Here we identify two additional essential genes on cp26, bbb26 and bbb27, through a systematic attempt to inactivate each open reading frame (ORF). Furthermore, an incompatible plasmid carrying resT, bbb26 and bbb27 could displace cp26. Computational and experimental analyses suggested that both BBB26 and BBB27 are membrane-associated, periplasmic proteins. These data indicate that bbb26 and bbb27 encode essential but possibly redundant functions and that one or the other of these cp26 genes, in addition to resT, is required for bacterial viability. We conclude that the genetic linkage of critical physiological and virulence functions on cp26 is pertinent to its stable maintenance throughout the evolution of B. burgdorferi. [ABSTRACT FROM AUTHOR]

An interview with Tim Miles, former chief executive officer of Vodafone New Zealand is presented. He describes his approach to decision-making. He discusses how doing the thing that scares one most could reap rewards. He relates a technique he uses to humanise management theory. He offers information on the employee recognition programme he introduced in Vodafone UK.

The article examines the conflict between profits and business ethics in New Zealand. Information on the decision of Solid Energy to pay spies to report on the international operations of its enemy Save Happy Valley Coalition, is presented. Details of the allegations against Mercury Energy concerning the death of Folole Muliaga are outlined. An overview of the activities of state-owned enterprise to make profits at the expense of public good is provided.

An interview with Lynda Reid, principal of Saint Cuthbert's College in Auckland, New Zealand, is presented. She shares her views on the role of parents and the role of stakeholders in the operations of the school. She relates how she manages the staff of the school. She describes the ways by which she mentors others.

Borrelia burgdorferi, the aetiological agent of Lyme disease, follows a life cycle that involves passage between the tick vector and the mammalian host. To investigate the role of the 36 kb linear plasmid, lp36 (also designated the B. burgdorferi K plasmid), in the infectious cycle of B. burgdorferi, we examined a clone lacking this plasmid, but containing all other plasmids known to be required for infectivity. Our results indicated that lp36 was not required for spirochete survival in the tick, but the clone lacking lp36 demonstrated low infectivity in the mammal. Restoration of lp36 to the mutant strain confirmed that the infectivity defect was due to loss of lp36. Moreover, spirochetes lacking lp36 exhibited a nearly 4-log increase in ID50 relative to the isogenic lp36+ clone. The infectivity defect of lp36-minus spirochetes was localized, in part, to loss of the bbk17 ( adeC) gene, which encodes an adenine deaminase. This work establishes a vital role for lp36 in the infectious cycle of B. burgdorferi and identifies the bbk17 gene as a component of this plasmid that contributes to mammalian infectivity. [ABSTRACT FROM AUTHOR]

STAT-1 plays a role in mediating stress responses to various stimuli and has also been implied to be a tumour suppressor. Here, we report that STAT-1-deficient cells have defects both in intra-S-phase and G2-M checkpoints in response to DNA damage. Interestingly, STAT-1-deficient cells showed reduced Chk2 phosphorylation on threonine 68 (Chk2-T68) following DNA damage, suggesting that STAT-1 might function in the ATM-Chk2 pathway. Moreover, the defects in Chk2-T68 phosphorylation in STAT-1-deficient cells also correlated with reduced degradation of Cdc25A compared with STAT-1-expressing cells after DNA damage. We also show that STAT-1 is required for ATM-dependent phosphorylation of NBS1 and p53 but not for BRCA1 or H2AX phosphorylation following DNA damage. Expression levels of BRCT mediator/adaptor proteins MDC1 and 53BP1, which are required for ATM-mediated pathways, are reduced in cells lacking STAT-1. Enforced expression of MDC1 into STAT-1-deficient ceils restored ATM-mediated phosphorylation of downstream substrates. These results imply that STAT-1 plays a crucial role in the DNA-damage-response by regulating the expression of 53BP1 and MDC1, factors known to be important for mediating ATM-dependent checkpoint pathways. [ABSTRACT FROM AUTHOR]

We previously reported that prenatal and suckling exposure to a maternal diet rich in animal fat leads to cardiovascular dysfunction in young adult rat offspring with subsequent development of dysfipidemia and hyperglycemia. We have further investigated glucose homeostasis in adult female offspring by euglycemic-hyperinsulinemic clamp and by dynamic assessment of glucose-stimulated insulin secretion in isolated, perifused pancreatic islet cells. Additionally, given the link between reduced mitochondrial DNA (mtDNA) content and the development of type 2 diabetes mellitus, we have measured mtDNA in organs from young adult animals. Sprague­Dawley rats were fed a diet rich in animal fat or normal chow throughout pregnancy and weaning. Infusion of insulin (5 mU·kg-1·min-1) resulted in a higher steady-state plasma insulin concentration in 1-year-old offspring of fat-fed dams (OHF, n = 4) vs. offspring of control dams (OC, n = 4, P < 0.01). Glucose-stimulated insulin secretion in isolated islets from 9-mo-old OHF was significantly reduced compared with OC (n = 4, P < 0.05). Transmission electron micrography showed altered insulin secretory granule morphology in OHF pancreatic β-cells. Kidney mtDNA was reduced in 3-mo-old OHF [16S-to-18S gene ratio: OC (n = 10) 1.05 ± 0.19 vs. OHF (n = 10) 0.66 ± 0.06, P < 0.05]. At 6 mo, gene chip microarray of OHF aorta showed reduced expression of the mitochondrial genome. Prenatal and suckling exposure to a diet rich in animal fat leads to whole body insulin resistance and pancreatic β-cell dysfunction in adulthood, which is preceded by reduced tissue mtDNA content and altered mitochondrial gene expression. [ABSTRACT FROM AUTHOR]

The corticotrophin-releasing hormone-related factor, urocortin (Ucn) and the interleukin (IL)-6 family cytokine cardiotrophin-1 (CT-1) are both cardioprotective agents able to protect the heart from ischemic damage. In both cases the protective effect involves activation of the p42/p44 MAPK and PI-3 kinase/Akt pathways, but the protective effect of Ucn requires de novo protein synthesis whereas that of CT-1 does not. In this study, we show that Ucn induces enhanced expression of CT-1 at both the mRNA and protein levels. This effect is mediated by activation of the CT-1 gene promoter and requires the transcription factor C/EBPβ/NF-IL6. Hence, a specific cardioprotective factor can induce enhanced expression of another cardioprotective factor belonging to an unrelated protein family. [ABSTRACT FROM AUTHOR]