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Canine vector-borne infections (CVBIs) are a global health problem. The military working dogs of Sri Lanka die at an early age, and CVBIs have been a leading speculated cause. We examined CVBIs in the working dogs of the Sri Lanka air force (SLAF) and free-roaming dogs (FRDs) and privately owned dogs (PODs) country-wide. Giemsa-stained smears were prepared and conventional PCR-positive DNA was subjected to sequencing and phylogeny. Of the 668 dogs sampled, 212 (31.7%) had one or more CVBIs. The prevalence of infections among the FRDs (40.0%) was significantly higher than SLAF working dogs (30.0%; χ2 = 10.5216; p = 0.0012) and PODs (26.2%; χ2 = 5.3414, p = 0.0208) but not between SLAF dogs and PODs (χ2 = 1.7655, p = 0.1838). Many infected dogs were asymptomatic (57.4%), which was higher among the FRDs. Seven infectious agents were identified: Babesia gibsoni, B. canis, Ehrlichia canis, Anaplasma platys, Leishmania sp., Hepatozoon canis, and filaria worms. The most common infection was B. gibsoni (13.8%), followed by E. canis (9.9%). Three tick species: Rhipicephalus linneai, Rhipicephalus haemaphysaloides and Haemophysalis bispinosa were found infesting the dogs. The SLAF dogs were thoroughly quarantined upon arrival, but the infection prevalence was similar to PODs. [ABSTRACT FROM AUTHOR]

Despite tea [Camellia sinensis (L.) O. Kuntze] is one of the top non-alcoholic beverages consumed around the world; its genetic and phenotypic diversity is less understood compared to other plantation crops. The study's aims were to undertake phenotypic and genotypic characterization of Sri Lankan and Indian tea germplasm and to identify diverse accessions to accelerate tea breeding programmes in both countries. A total of 171 tea accessions, comprising 94 Sri Lankan and 77 Indian accessions were used. All the accessions were subjected to phenotyping and genotyping using 28 polymorphic simple sequence repeat (SSR) markers. Based on 16 morphological characters, the first three principal components explained 57.61% and 58.43% of the total variability of Sri Lankan and Indian accessions, respectively. Young shoot pubescence, young shoot pigmentation, serration of leaf margin, and mature leaf colour contributed positively to the grouping of accessions. Based on Neighbor-joining analysis, all Sri Lankan accessions grouped in a single cluster, whereas Indian accessions grouped in two distinct clusters. The Gower's distance method was the most appropriate than other methods for developing core subsets. Among 21 Sri Lankan core accessions selected, 11 accessions belong to introductions, five TRI-developed cultivars and five estate selections. Among 18 Indian core accessions selected, 11 belong to China types, two Assam types and five Indian recommended cultivars. The current study is the first study to compare tea germplasm of both countries and the results are useful for tea crop improvement programme, conservation and utilization of tea germplasm in India and Sri Lanka in the future. [ABSTRACT FROM AUTHOR]

The donor–acceptor (D-A) type of conjugated polymers has emerged as the paradigm of the third generation of electronically conducting polymers demonstrating improved infrared activity and intrinsic electronic conductivity. Judicious selection of donor (D) and acceptor (A) monomers for copolymerization can further fine-tune these properties. Notably, for such refinement, natural compounds provide many conjugated molecules with various functional groups. Berberine cation (Ber+) found in Coscinium fenestratum has extensive conjugation and contains both an electron deficient isoquinolium A moiety and electron-rich D-type methylenedioxy and methoxy groups. The incorporation of natural products in electronic materials is a novel area of research which opens a wide scope for future electronic and optoelectronic devices. Investigation of their fundamental properties via computer simulations is therefore important. In this study, quantum chemical calculations are performed using density functional theory (DFT) to investigate the electronic and optical properties of oligomers of Ber+ and 3,4-ethylenedioxythiophene (EDOT) and to explore the possibilities for homo-polymerization of Ber+ and its copolymerization with EDOT. It has been revealed that homo-polymerization is not favoured but copolymerization with EDOT is possible. As such, Ber+ was copolymerized with EDOT and the copolymers formed by electro-polymerization are extensively characterised and the D-A behaviour of the copolymers verified. Furthermore, the theoretical predictions have been compared with the experimental data. [ABSTRACT FROM AUTHOR]

Dendritic spines are small, dynamic protrusions along the dendrite that comprise more than 90% of excitatory connections in the brain, making them essential sites for neuronal communication. These synaptic sites change throughout the process of development, reducing in density and shifting morphology as synapses are refined. One important class of dendritic spine regulators is microRNA (miRNA), small-noncoding RNAs that post-transcriptionally regulate gene expression. Several studies suggest that miRNA-324-5p regulates dendritic spine formation. In addition, we have previously shown that miR-324-5p plays a role in seizure and long-term potentiation, both of which involve dendritic spine changes. In this study, we aimed to characterize the role of miRNA-324-5p in developmental spine regulation by assessing the effect of Mir324 knockout (KO) on dendritic spine density and expression of a subset of dendritic proteins at select developmental time points. We show that miR-324-5p expression is developmentally regulated and peaks at 4 weeks of age. We demonstrate that loss of miR-324-5p expression leads to differential changes in both target protein expression and spine density at different time points during development, disrupting the pattern of spine density changes and leading to a premature loss of dendritic spines in KO mice, which is compensated later. Our findings indicate that miR-324-5p plays a role in synaptic refinement across development. Additionally, our data illustrate the importance of context in the study of miRNA, as regulation by and/or of miRNA can vary dramatically across development and in disease. [ABSTRACT FROM AUTHOR]

Purpose: Babesiosis is one of the most important globally extended and quickly spreading tick-borne infections of dogs. Diagnosis of babesiosis in Sri Lanka is based on clinical signs followed by thin blood smears which could be error-prone due to undetected early infections, absence of clinical signs or low parasitemia. The present study investigated the prevalence of babesiosis in dogs presented to the Veterinary Teaching Hospital (VTH) at the Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, for treatments, vaccinations, and regular check-ups, and compared the diagnosis methods of microscopy and molecular analysis. Methods: Blood samples from dogs were collected from January to June 2019. First, Giemsa stained blood smears were prepared, and then the blood samples were subjected to PCR using genus-specific primers to amplify a 411–450 bp region in the 18S rRNA gene. Twenty samples from PCR amplified products were sequenced for species identification and phylogenetic analysis. Clinical signs of the dogs were noted down, and ticks were also collected from dogs if any. Results: Results show a very high prevalence of canine babesiosis (78.6%) among the dogs brought to the VTH. The parasite was identified microscopically and genetically as Babesia gibsoni. A large percentage (66.7%) of infections was asymptomatic. Out of 42 blood samples, 19 (45.2%) were microscopically positive for babesiosis while 33 (78.6%) were PCR positive, showing a significant difference in the two methods of diagnosis (chi-square test, χ2 = 9.462, p = 0.002). Three tick species: Rhipicephalus haemaphysaloides, Haemaphysalis bispinosa, and Rhipicephalus sanguineus were found attached to the dogs. Conclusion: This study shows a very high prevalence of canine babesiosis among dogs in the Kandy area. Most of these infections might go undetected if only microscopy was used to diagnose. An improved, rapid diagnostic method such as the novel, PCR-based point-of-care diagnostic method that detects very low parasitemia within 30 min is needed. Moreover, as most infected dogs did not show clinical signs, they may act as reservoirs of infection. The ability of asymptomatic dogs to spread babesiosis should be investigated. [ABSTRACT FROM AUTHOR]

Fluoride is a beneficial trace element for human health as its deficiency and excess levels can cause detrimental health effects. In Sri Lanka, dry zone regions can have excessive levels of fluoride in drinking water and can cause dental and skeletal fluorosis. In addition to drinking water, traditional habits of tea consumption can cause an additional intake of fluoride in the population. A total number of 39 locally blended black tea samples were collected from a village where chronic kidney disease with undetermined origin (CKDu) is prevalent. In addition, unblended tea samples were obtained from tea-producing factories. The fluoride contents in infusions of 2% weight per volume (w/v) were measured using calibrated ion-selective fluoride electrodes. The mean fluoride content was 2.68±1.03 mg/L in loose tea, 1.87±0.57mg/L in packed tea samples, and 1.14±0.55 mg/L in unblended tea. Repeated brewing of the same tea leaves showed that over 50% of fluoride leached into the solution in the first infusion. An estimate of the daily total average fluoride intake via tea consumption per person is 2.68 mg per day. With groundwater in many dry zone regions in Sri Lanka showing high fluoride levels that exceed 0.5 mg/L, the additional daily intake can rapidly exceed recommended thresholds of 2 mg/day. This can add to adverse health impacts that might also relate to CKDu. [ABSTRACT FROM AUTHOR]

Purpose: To outline the process of the STABILISE technique and its use; reporting patient outcomes and midterm follow up for complicated aortic dissection. Materials and methods: Single centre retrospective analysis from January 2011 to January 2021 using the STABILISE technique which utilises balloon assistance to facilitate intimal disruption and promote aortic relamination. Results: Sixteen patients underwent endovascular aortic repair with the STABILISE technique for aortic dissection over the study period. Fourteen patients (14/16; 88%) had acute dissection. Two of 16 (12%) were chronic. The median age of the patient cohort was 61 years (range 32–80 years) and consisted of a male majority (n = 11; 69%). The median time from diagnosis to intervention was 5 days (1–115 days; IQR 1–17.3). More than half (56%) had surgical repair of a acute type A aortic dissection prior to radiological intervention. The procedure was technically successful with no procedural mortality. Two patients were lost to follow up and two died in the post-operative period. Twelve patients had ongoing follow up with an average number of 2.9 ± 1.6 scans performed. Follow up was available in thirteen patients (81%) with a median follow up period of 1097 days (IQR 707–1657). The rate of re-intervention (n = 2/16; 13%) requiring additional stenting was in line with published re-intervention data (15%). Follow up showed a reduction in false lumen size following treatment with total luminal dimensions remaining stable over the follow-up period. Conclusion: The STABILISE technique as a procedure for complicated aortic dissection, either acute or chronic, appears safe with stable mid-term aortic remodelling and patient outcomes. Level of evidence: Level 3, Retrospective cohort study. [ABSTRACT FROM AUTHOR]

Cell penetrating peptides (CPPs) hold immense potential for the transport of therapeutic agents to their active targets, due to their low cytotoxicity and high transduction efficiency. Adoption of CPPs as delivery systems, and development of novel peptides has been hampered by the variety of mechanisms and complexity of factors involved in cellular uptake. Quantitatively analyzing these systems is further hindered by the inability to compare data among reports due to varying experimental conditions. In this study we investigate the translocation of seventeen CPPs, representing cationic, amphipathic and hydrophobic physicochemical classes, through a DOPC membrane using molecular dynamics simulations. Free energy profiles for individual peptides inserting into the lipid bilayer were generated giving insight into both the approach and adsorption of different CPPs to cell membranes, and the feasibility of their direct translocation. The control of physical conditions and composition allows objective comparison of different peptides and analyze the effect of sequence on the adsorption and translocation energetics. Our results indicate that positively charged residues impart repulsion, while hydrophobic residues increase bilayer interaction. This study is the first step in fully understanding the processes and energetics involved in the passive translocation mechanisms of CPPs, which usually involve multiple peptides. [ABSTRACT FROM AUTHOR]

Purpose: Arteriovenous malformations (AVMs) are abnormal communications between arteries and veins without an intervening capillary system. The best endovascular treatment option for these is unclear and may involve multiple staged procedures using a variety of embolic materials. We report our initial experience using a modified version of a previously published neurointerventional technique to treat soft tissue AVMs with single-stage curative intent. Materials and methods: Soft tissue AVMs treated endovascularly using either sole arterial or combined arterial and venous balloon-assisted techniques with liquid embolic agents were retrospectively identified over a 3.5 year period (January 2017 to June 2020)) at two centres. Clinical, pre-operative radiological, procedural technical and post treatment details were recorded. Results: Seven patients were treated for symptomatic soft tissue arteriovenous malformations. These AVMs were located in the peripheral limbs (five), tongue (one) and uterus (one). Curative treatment was achieved in 6/7 patients with one patient requiring a second treatment approximately 1 year later. A variety of liquid embolisation agents (LEAs) including sclerosants and polymers were used. Clinical success rate was 100% following treatment. One patient experienced expected temporary post-operative tongue swelling requiring tracheostomy occurred following embolisation of the lingual AVM. A minor complication in a second patient was due to an access site haematoma developed following treatment of the hand AVM requiring surgical intervention. No long-term sequelae or additional complications were observed. Conclusion: Endovascular arterial and venous balloon assisted LEA embolization of soft tissue AVMs with curative intent is feasible. This technique may provide an alternative treatment option for achieving durable occlusion for complex soft tissue AVMs. [ABSTRACT FROM AUTHOR]

Background: Visceral and renal artery aneurysms (VRAAs) are uncommon but are associated with a high mortality rate in the event of rupture. Endovascular treatment is now first line in many centres, but preservation of arterial flow may be difficult in unfavourable anatomy including wide necked aneurysms, parent artery tortuosity and proximity to arterial bifurcations. Endovascular stenting, and in particular flow-diversion, is used in neurovascular intervention to treat intracranial aneurysms but is less often utilised in the treatment of VRAAs. The CASPER stent is a low profile dual-layer braided nitinol stent designed for carotid stenting with embolic protection and flow-diversion properties. We report the novel use of the CASPER stent for the treatment of VRAAs. We present a case series describing the treatment of six patients with VRAAs using the CASPER stent. Results: Six patients with unruptured VRAAs were treated electively. There were three splenic artery aneurysms and three renalartery aneurysms. Aneurysms were treated with the CASPER stent, with or without loose aneurysm coil packing or liquid embolic depending on size and morphology. All stents were successfully deployed with no immediate or periprocedural complications. Four aneurysms completely occluded after serial imaging follow up with one case requiring repeat CASPER stenting for complete occlusion. In one patient a single aneurysm remained patent at last follow up, A single case was complicated by delated splenic infarction and surgical splenectomy. Conclusion: Preliminary experience with the CASPER stent suggests it is technically feasible and effective for use in the treatment of VRAAs. [ABSTRACT FROM AUTHOR]

Among the many contributions Gerald made he will perhaps be best remembered for his work there in isolating and characterizing the thick filament accessory protein, myosin binding protein C (MyBP-C). 1 Bennett P, Craig R, Starr R, Offer G. The ultrastructural location of C-protein, X-protein and H-protein in rabbit muscle. 5 Moos C, Offer G, Starr R, Bennett P. Interaction of C-protein with myosin, myosin rod and light meromyosin. 27 Yu LC, Xu S, Gu J, White HD, Offer G. Helical order in myosin filaments and evidence for one ligand inducing multiple myosin conformations. [Extracted from the article]

Tea (Camellia sinensis L.) is the most widely-consumed beverage in the world. The biochemical components of tea leave include polyphenols (catechins and flavonoides), alkaloids (caffeine, theobromine, theophylline, etc.), volatile compounds, polysaccharides, amino acids, lipids and vitamins show a variety of bioactivities. Prolong cross-pollination nature of tea plants have produced considerable heritable variation, resulting in a high level of genetic diversity. The collection and conservation of the cultivars, landraces and wild relatives of the tea plant provides breeders with fundamental materials from which new cultivars are to be developed. The major role of tea breeding is to improve productivity, enhance tolerant to biotic and abiotic stress, and increase tea flavor and quality. Dissection of the genetic basis of these traits provides the potential for accelerating the breeding process by developing new tools such as marker-assisted selection. Therefore present review provides an overview of the biochemical and metabolite diversity of the global tea germplasm and its characterization and utilization. [ABSTRACT FROM AUTHOR]

Opinion Statement: Spinal metastases are the most commonly encountered tumour of the spine, occurring in up to 40% of patients with cancer. Each year, approximately 5% of cancer patients will develop spinal metastases. This number is expected to increase as the life expectancy of cancer patients increases. Patients with spinal metastases experience severe and frequently debilitating pain, which often decreases their remaining quality of life. With a median survival of less than 1 year, the goals of treatment in spinal metastases are reducing pain, improving or maintaining level of function and providing mechanical stability. Currently, conventional treatment strategies involve a combination of analgesics, bisphosphonates, radiotherapy and/or relatively extensive surgery. Despite these measures, pain management in patients with spinal metastases is often suboptimal. In the last two decades, minimally invasive percutaneous interventional radiology techniques such as vertebral augmentation and radiofrequency ablation (RFA) have shown progressive success in reducing pain and improving function in many patients with symptomatic spinal metastases. Both vertebral augmentation and RFA are increasingly being recognised as excellent alternative to medical and surgical management in carefully selected patients with spinal metastases, namely those with severe refractory pain limiting daily activities and stable pathological vertebral compression fractures. In addition, for more complicated lesions such as spinal metastasis with soft tissue extension, combined treatments such as vertebral augmentation in conjunction with RFA may be helpful. While combined RFA and vertebral augmentation have theoretical benefits, comparative trials have not been performed to establish superiority of combined therapy. We believe that a multidisciplinary approach as well as careful pre-procedure evaluation and imaging will be necessary for effective and safe management of spinal metastases. RFA and vertebral augmentation should be considered during early stages of the disease so as to maintain the remaining quality of life in this patient population group. [ABSTRACT FROM AUTHOR]

Introduction: Visceral and renal artery aneurysms (VRAAs) are an uncommon clinical entity but carry a risk of rupture with associated morbidity and mortality. The rupture risk is particularly high when the aneurysms are large, of unfavourable morphology or in the setting of pregnancy and perioperative period. Endovascular approaches are now first line in the treatment of VRAA, but conventional techniques may be ineffective in excluding aneurysms with unfavourable anatomy such as those with wide necks or at arterial bifurcation points. The neurovascular Comaneci neck-bridging device is used to temporarily cover the neck of intracranial aneurysms without occluding forward arterial flow during endovascular coiling. We report the novel use of the Comaneci neck-bridging device for the treatment of complex peripheral VRAAs.Materials and Methods: We describe the treatment of two patients with renal and splenic artery aneurysms demonstrating unfavourable anatomic morphology for conventional endovascular approaches.Results: In the first patient, the renal artery aneurysm was situated at the intrarenal bifurcation of the main renal artery in the setting of a solitary kidney. In the second patient, the splenic artery aneurysm was situated close to the splenic hilum at the distal splenic arterial bifurcation. The Comaneci neck-bridging device was successfully used in both cases to assist coil embolisation with visceral preservation.Conclusions: The Comaneci neck-bridging device is potentially safe and effective for the treatment of peripheral VRAA with unfavourable anatomic characteristics that would have been deemed unsuitable for treatment using conventional techniques.Level Of Evidence: Level 4, Technical Report. [ABSTRACT FROM AUTHOR]

In this paper we study the use of human robot interaction as a mean to objectively evaluate imitation deficits in children with autism. Robot control and data analysis methods were combined to assess the quality of interaction between the robot and the subjects. Humanoid robot Zeno was used to execute upper body gestures which the subjects were asked to imitate. The resulting motion of the subject was acquired through a motion capture system and compared with the intended motion performed by Zeno using the dynamic time warping (DTW) algorithm. During this study, the clinical hypothesis was that the resulting DTW cost can serve as a quantitative measure for the similarity between the motions, and thus can be used to objectively assess the severity of imitation deficits exhibited by the child. To validate this hypothesis, we present two sets of experiments, one with a set of healthy adults and the other with a group of children, some with autism spectrum disorder. The experiment with adult subjects serves as a statistically significant test to demonstrate the viability of the DTW cost as a similarity measure for the gesture analysis, whereas the experiment with child subjects is a pilot study to differentiate imitation performance for children with autism. [ABSTRACT FROM AUTHOR]

Purpose: To describe the natural history of liver adenomatosis (LA), including complications and changes in lesion size over time. Materials and methods: Eighteen patients with clinical diagnosis of LA were included. Clinical and biochemical information were collected. The initial and follow-up MR studies were reviewed retrospectively to determine change in lesion size and imaging features. Results: Seventeen patients were women (94.4%). The mean age of the initial MR study was 37.0 years (18-52 years). The median size of the largest lesion was 6.7 cm (range 3.0-13.5 cm). Intratumoral bleeding was detected on MRI in 9 lesions, in 7 patients (38.8%). The median size for hemorrhagic lesions was 7.6 cm (range 4.1-13.5 cm). During the mean follow-up period of 29.4 (range 4-98) months, 10 patients had stable disease (55.6%), and 8 patients had tumor regression (44.4%). Of 8 patients who were followed without intervention, 3 patients (37.5%) had spontaneous regression. No malignant transformation or lesion progression was occurred. Conclusion: During an over 2-year follow-up period, the majority of lesions of LA appeared to remain stable or showed tumor regression. Spontaneous tumor regression can be observed in approximately 37% of individuals in the age range of 28-53 years. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine the temperature dependence of active force in lengthening and shortening muscle. Experiments were done, in vitro, on bundles of intact fibres (fibre length L ~2 mm; sarcomere length ~2.5 μm) isolated from a rat fast muscle (flexor hallucis brevis) and a ramp length change of 5-7 % L was applied on the plateau of an isometric tetanic contraction. Ramp lengthening increased and ramp shortening decreased the muscle tension to new approximately steady levels in a velocity-dependent way. The isometric tension and the lower steady tension reached at a given shortening velocity, increased with warming from 10 to 35 °C and the relation between tension and reciprocal absolute temperature was sigmoidal. However, the tension-temperature curve of shortening muscle was sharper and shifted to higher temperature with increased velocity. In contrast, the enhanced steady tension during lengthening at a given velocity was largely temperature-insensitive within the same temperature range; we hypothesize that the tension-temperature curve may be shifted to lower temperatures in lengthening muscle. Consequently, when normalised to the isometric tension at each temperature, the tension during lengthening at a given velocity decreased exponentially with increase of temperature. The residual force enhancement that remains after ramp lengthening showed a similar behaviour and was markedly reduced in warming from 10 to 35 °C. The findings are consistent with the thesis that active force generation in muscle is endothermic and strain-sensitive; during shortening with a faster crossbridge cycle it becomes more pronounced, but during lengthening it becomes depressed as the cycle slows in a velocity-dependent way. The residual force enhancement may be caused by the same process in addition to non-crossbridge mechanism(s). [ABSTRACT FROM AUTHOR]

Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials were intrinsically generated by immature IHCs of altricial rodents and that apical IHCs showed bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter acetylcholine fine-tunes the IHC's resting membrane potential (Vm), and as such is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the Vm of apical and basal IHCs by triggering small-conductance Ca2+-activated K+ (SK2) channels. We propose that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway. [ABSTRACT FROM AUTHOR]

The stiffness of myosin heads attached to actin is a crucial parameter in determining the kinetics and mechanics of the crossbridge cycle. It has been claimed that the stiffness of myosin heads in the anterior tibialis muscle of the common frog (Rana temporaria) is as high as 3.3 pN/nm, substantially higher than its value in rabbit muscle (~1.7 pN/nm). However, the crossbridge stiffness measurement has a large error since the contribution of crossbridges to half-sarcomere compliance is obtained by subtracting from the half-sarcomere compliance the contributions of the thick and thin filaments, each with a substantial error. Calculation of its value for isometric contraction also depends on the fraction of heads that are attached, for which there is no consensus. Surprisingly, the stiffness of the myosin head from the edible frog, Rana esculenta, determined in the same manner, is only 60% of that in Rana temporaria. In our view it is unlikely that the value of such a crucial parameter could differ so substantially between two frog species. Since the means of the myosin head stiffness in these two species are not significantly different, we suggest that the best estimate of the stiffness of the myosin heads for frog muscle is the average of these data, a value similar to that for rabbit muscle. This would allow both frog and rabbit muscles to operate the same low-cooperativity mechanism for the crossbridge cycle with only one or two tension-generating steps. We review evidence that much of the compliance of the myosin head is located in the pliant region where the lever arm emerges from the converter and propose that tension generation ('tensing') caused by the rotation and movement of the converter is a separate event from the passive swinging of the lever arm in its working stroke in which the strain energy stored in the pliant region is used to do work. [ABSTRACT FROM AUTHOR]

Carcinomatous polyarthritis (CP) is a rare paraneoplastic disorder that has been associated with a variety of solid tumors. It presents in a similar manner to other polyarticular disorders and often precedes detection of the underlying malignancy, making recognition critical. CP responds to the treatment of the neoplastic process. We present a patient who initially presented with asymmetric inflammatory polyarthritis who was later diagnosed with bronchogenic carcinoma. Following the case report we present our learning objectives, which include the differential diagnosis of inflammatory polyarthritis, diagnostic approach to CP, and features that distinguish it from other more common causes of polyarthritis. We conclude with a brief discussion of the pathophysiology and management of CP. [ABSTRACT FROM AUTHOR]

Interleukin-10 (IL-10) is intensely studied, yet little is known about the mechanisms that control IL-10 expression. We identified striking similarities between IL-10 and interferon-γ (IFN-γ) regulation in mouse natural killer (NK) cells. Like IFN-γ, IL-10 expression is induced by IL-2 and IL-12 and IL-2+IL-12 stimulation is synergistic. Unlike IFN-γ, neither IL-18 nor Ly-49D cross-linking induced IL-10 expression however. Additionally, the IL-12 homologs IL-23 and IL-27 also do not regulate NK cell-specific IL-10. We determined that a small population of NK cells accounts for IL-10 production. The induction of IL-10 by IL-2+IL-12 treatment in NK cells appears to be biphasic, with an initial burst of expression which diminishes by 12 h but spikes again at 18 h. We determined that much like IFN-γ, Stat4 is largely required for IL-12-induced IL-10. Conversely, we observed normal induction of IL-10 in T-bet-deficient NK cells. We identified a Stat4-binding element in the fourth intron of the Il10 gene, which is completely conserved between mouse and human. This intronic Stat4 motif is within a conserved noncoding sequence, which is also a target for cytokine-induced histone acetylation. These findings highlight tissue- and receptor-specific IL-10 regulatory mechanisms, which may be part of an early feedback loop.Genes and Immunity (2008) 9, 316–327; doi:10.1038/gene.2008.20; published online 10 April 2008 [ABSTRACT FROM AUTHOR]

Woolly apple aphid (WAA; Eriosoma lanigerum Hausm.) can be a major economic problem to apple growers in most parts of the world, and resistance breeding provides a sustainable means to control this pest. We report molecular markers for three genes conferring WAA resistance and placing them on two linkage groups (LG) on the genetic map of apple. The Er1 and Er2 genes derived from ‘Northern Spy’ and ‘Robusta 5,’ respectively, are the two major genes that breeders have used to date to improve the resistance of apple rootstocks to this pest. The gene Er3, from ‘Aotea 1’ (an accession classified as Malus sieboldii), is a new major gene for WAA resistance. Genetic markers linked to the Er1 and Er3 genes were identified by screening random amplification of polymorphic deoxyribonucleic acid (DNA; RAPD) markers across DNA bulks from resistant and susceptible plants from populations segregating for these genes. The closest RAPD markers were converted into sequence-characterized amplified region markers and the genome location of these two genes was assigned to LG 08 by aligning the maps around the genes with a reference map of ‘Discovery’ using microsatellite markers. The Er2 gene was located on LG 17 of ‘Robusta 5’ using a genetic map developed in a M.9 × ‘Robusta 5’ progeny. Markers for each of the genes were validated for their usefulness for marker-assisted selection in separate populations. The potential use of the genetic markers for these genes in the breeding of apple cultivars with durable resistance to WAA is discussed. [ABSTRACT FROM AUTHOR]

Abstract  We examined, over a wide range of temperatures (10–35°C), the isometric tension and tension during ramp shortening at different velocities (0.2–4 L 0/s) in tetanized intact fibre bundles from a rat fast (flexor hallucis brevis) muscle; fibre length (L 0) was 2.2 mm and sarcomere length ~2.5 μm. During a ramp shortening, the tension change showed an initial inflection of small amplitude (P 1), followed by a larger exponential decline towards an approximate steady level; the tension continued to decline slowly afterwards and the approximate steady tension at a given velocity was estimated as the tension (P 2) at the point of intersection between two linear slopes, as previously described (Roots et al. 2007). At a given temperature, the tension P 2 declined to a lower level and at a faster rate (from an exponential curve fit) as the shortening velocity was increased; the temperature sensitivity of the rate of tension decline during ramp shortening at different velocities was low (Q 10 0.9–1.5). The isometric tension and the P 2 tension at a given shortening velocity increased with warming so that the relation between tension and (reciprocal) temperature was sigmoidal in both. In isometric muscle, the temperature T 0.5 for half-maximal tension was ~10°C, activation enthalpy change (∆H) was ~100 kJ mol−1 and entropy change (∆S) ~350 J mol−1 K−1. In shortening, these were increased with increase of velocity so that at a shortening velocity (~4 L 0/s) producing maximal power at 35°C, T 0.5 was ~28°C, ∆H was ~200 kJ mol−1 and ∆S ~ 700 J mol−1 K−1; the same trends were seen in the tension data from isotonic release experiments on intact muscle and in ramp shortening experiments on maximally Ca-activated skinned fibres. In general, our findings show that the sigmoidal relation between force and temperature can be extended from isometric to shortening muscle; the implications of the findings are discussed in relation to the crossbridge cycle. The data indicate that the endothermic, entropy driven process that underlies crossbridge force generation in isometric muscle (Zhao and Kawai 1994; Davis, 1998) is even more pronounced in shortening muscle, i.e. when doing external work. [ABSTRACT FROM AUTHOR]

Abstract  We examined the tension responses to ramp shortening and lengthening over a range of velocities (0.1–5 L 0/s) and at 20�C and 30�C in tetanized intact fibre bundles from a rat fast (flexor hallucis brevis) muscle; fibre length (L 0) was 2.2 mm and sarcomere length ∼2.5 μm. The tension change during ramp releases as well as ramp stretches showed an early transition (often appearing as an inflection) at 1–4 ms; the tension change at this transition and the length change at which it occurred increased with velocity. A second transition, indicated by a more gradual reduction in slope, occurred when the length had changed by 14–28 nm per half-sarcomere; the tension at this transition increased with lengthening velocity towards a plateau and it decreased with shortening velocity towards zero tension. The velocity dependence of the time to the transitions and the length change at the transitions showed some asymmetries between shortening and lengthening. Based on analyses of the velocity dependence of the tension and modelling, we propose that the first transition reflects the tension change associated with the crossbridge power stroke in shortening, or with the reversal of the power stroke in lengthening. Modelling shows that the reduction in slope at the second transition occurs when most of the crossbridges (myosin heads) that were attached at the start of the ramp become detached. After the second transition, the tension reaches a steady level in the model whereas the tension continues to increase during lengthening and continues to decrease during shortening in the experiments; this continuous tension change is seen at a wide range of initial sarcomere lengths and when active force is reduced by the myosin inhibitor, BTS. The continuous tension decline during shortening is not abolished by caffeine, but the rate of decline is reduced when the active force is depressed by BTS. We propose that stiffening of non-crossbridge visco-elastic elements upon activation contributes to the continuous tension rise during lengthening and the release of such tension and Ca-insensitive deactivation contribute to the tension decline during shortening in muscle fibres. [ABSTRACT FROM AUTHOR]

Giant cell arteritis predominantly affects cranial arteries and rarely involves other sites. We report a patient who presented with small bowel obstruction because of infarction from mesenteric giant cell arteritis. She had an unusual cause of her obstruction and a rare manifestation of giant cell arteritis. In spite of aggressive therapy with steroids, she died a month later because of multiple complications. We discuss the diagnosis and management of small bowel obstruction and differential diagnosis of vasculitis of the gastrointestinal tract. We were able to find 11 cases of bowel involvement with giant cell arteritis in the English literature. This case report illustrates that giant cell arteritis can be a cause of small bowel obstruction and bowel infarction. In the proper clinical setting, vasculitides need to be considered early in the differential diagnosis when therapy may be most effective. [ABSTRACT FROM AUTHOR]

The suitability of large-fruited apple cultivars as alternative donors of powdery mildew resistance to the crabapples carrying major gene resistances was assessed. Five accessions with varying levels of mildew resistance (‘Dülmener Rosen', ‘Liberty', ‘Sciros', ‘Prima' and ‘Red Delicious') and one susceptible cultivar (‘Cox's Orange Pippin') were mated in a partial diallel design, and sub-sets of each seedling family were evaluated for three years at three New Zealand sites (Havelock North, Riwaka and Clyde) with different climatic conditions. There was a high correlation among the powdery mildew susceptibility scores of the individual seedlings over the three years, but disease levels varied among sites, with those at Clyde being the highest. All accessions with some resistance were found to confer additive resistance to their progenies to varying degrees depending on the climatic conditions of the sites, but findings suggest that progeny selection at Clyde will be sufficient for breeding purposes. The performance of the cultivar itself was not necessarily a good predictor of the level of resistance conferred to its progenies. The mostly negative genetic correlations between powdery mildew scores and fruit quality attributes suggest that selecting for powdery mildew resistance and desirable fruit quality traits may not be difficult. However, a larger number of families may be needed for more precise estimates of the genetic correlations to strengthen confidence in this conclusion. [ABSTRACT FROM AUTHOR]

The paper summarizes the development of numerical procedures for modeling bulk deformation process and preform designing techniques based on the upper bound elemental technique (UBET). UBET has a unique place where an approximate, but faster solution is needed for decision making. In designing and optimizing multistage forging and profile ring-rolling processes, an approximate solution can be used to identify the most influential process parameters. Once an optimum combination of process conditions are determined, computationally intensive, but more accurate finite element analysis can be used to verify and refine results. In this paper, UBET procedures for closed-die forging and profile ring rolling are highlighted. Experimental investigations are used to validate the model predictions. Also, the UBET-based preform design tool is presented as a process and die design tool for multistage forging processes. Application of these techniques is presented with evidence of effective material usage and extended overall die-life. [ABSTRACT FROM AUTHOR]

We have examined the effects of N-benzyl-p-toluene sulphonamide (BTS), a potent and specific inhibitor of fast muscle myosin-II, using small bundles of intact fibres or single fibres from rat foot muscle. BTS decreased tetanic tension reversibly in a concentration-dependent manner with half-maximal inhibition at ∼ ∼2 μM at 20 °C. The inhibition of tension with 10 μM BTS was marked at the three temperatures examined (10, 20 and 30 °C), but greatest at 10 °C. BTS decreased active muscle stiffness to a lesser extent than tetanic tension indicating that not all of the tension inhibition was due to a reduced number of attached cross-bridges. BTS-induced inhibition of active tension was not accompanied by any change in the free myoplasmic Ca2+ transients. The potency and specificity of BTS make it a very suitable myosin inhibitor for intact mammalian fast muscle and should be a useful tool for the examination of outstanding questions in muscle contraction. [ABSTRACT FROM AUTHOR]

We examined the tension responses induced by rapid temperature-jumps (T-jumps) applied at different times during twitch and tetanic contractions in small intact fibre bundles (5–10 fibres) isolated from a fast foot muscle (flexor hallucis brevis) of the rat. A rapid T-jump of 2–4°C was induced by a 0.2 ms infrared (λ = 1.32 μm) laser pulse applied to the fibre bundle immersed in a 50 μl trough of physiological saline, the temperature of which was clamped at different steady temperatures ranging from 10 to 30°C. In a tetanic contraction, the tension increased to the same steady level when a standard T-jump was applied at different intervals after the onset of stimulation; thus, with maximal activation, an enhanced force generation by T-jump leads to a new steady state. In a twitch contraction, a T-jump induced a large, potentiation of tension when it was applied during the rising phase. Whereas the twitch relaxation subsequent to a T-jump was faster in all cases, the amplitude of the twitch tension potentiation decreased as the T-jump was delayed with respect to the stimulus, and there was no increase of tension when a T-jump was placed on the relaxation phase of the twitch. The increase of tension induced by a T-jump applied on the rising phase resulted in peak tension that was greater than the tension in control twitches at the steady post-T-jump temperature; therefore tension was higher than that expected on the basis of steady state temperature dependence of twitch tension. Whether these effects on a twitch contraction arise from differential fibre-heating by a T-jump that leads to shortening and development of sarcomere length disorder etc remain unclear. However, the findings may be interpreted as indicating that twitch tension increment by a T-jump occurs when excitation (the action potential) leading to calcium release and thin filament activation occur at the low temperature, whereas the crossbridge force-generation processes (and Ca -uptake) proceed at the higher temperature. [ABSTRACT FROM AUTHOR]

Potassium (K) channels have a key role in the regulation of neuronal excitability. Over a hundred different subunits encoding distinct K channel subtypes have been identified so far. A major challenge is to relate these many different channel subunits to the functional K currents observed in native neurons. In this review, we have concentrated on cerebellar granule neurons (CGNs). We have considered each of the three principal super families of K channels in turn, namely, the six transmembrane domain, voltage-gated super family, the two transmembrane domain, inward-rectifier super family and the four transmembrane domain, leak channel super family. For each super family, we have identified the subunits that are expressed in CGNs and related the properties of these expressed channel subunits to the functional currents seen in electrophysiological recordings from these neurons. In some cases, there are strong molecular candidates for proteins underlying observed currents. In other cases the correlation is less clear. We show that at least 26 potassium channel subunits are moderately or strongly expressed in CGNs. Nevertheless, a good empirical model of CGN function has been obtained with just six distinct K conductances. The transient K A current in CGNs, seems due to expression of K V 4.2 channels or K V 4.2/4.3 heteromers, while the K Ca current is due to expression of large-conductance slo channels. The G-protein activated K IR current is probably due to heteromeric expression of K IR 3.1 and K IR 3.2. Perhaps K IR 2.2 subunits underlie the K IR current when it is constitutively active. The leak conductance can be attributed to TASK-1 and or TASK-3 channels. With less certainty, the I K-slow current may be due to expression of one or more members of the KCNQ or EAG family. Lastly, the delayed-rectifier K V current has as many as six different potential contributors from the extensive K V family of subunits. Since many of these subunits are highly regulated by neurotransmitters, physiological regulators and, often, auxiliary subunits, the resulting electrical properties of CGNs may be highly dynamic and subject to constant fine-tuning. [ABSTRACT FROM AUTHOR]

A homology model of the pore domain of the Shaker K[sup +] channel has been constructed using a bacterial K[sup +] channel, KcsA, as a template structure. The model is in agreement with mutagenesis and sequence variability data. A number of structural features are conserved between the two channels, including a ring of tryptophan sidechains on the outer surface of the pore domain at the extracellular end of the helix bundle, and rings of acidic sidechains close to the extracellular mouth of the channel. One of these rings, that formed by four Asp447 sidechains at the mouth of the Shaker pore, is shown by pK[sub A] calculations to be incompletely ionized at neutral pH. The potential energy profile for a K[sup +] ion moved along the central axis of the Shaker pore domain model selectivity filter reveals a shallow well, the depth of which is modulated by the ionization state of the Asp447 ring. This is more consistent with the high cation flux exhibited by the channel in its conductance value of 19 pS. [ABSTRACT FROM AUTHOR]

The giant muscle protein titin (connectin), contained in the gap filament that connect a thick filament to the Z-line in a sarcomere, is generally considered to be responsible for the passive force (tension) and visco-elasticity in resting striated muscle. However, whether it can account for all the features of the resting tension response remains unclear. In this paper, we examine the basic features of the ‘sarcomeric visco-elasticity’ in a single resting mammalian muscle fibre and attempt to account for various tension components on the basis of known structural features of a sarcomere. At sarcomere length of ∼2.6 μm, the force response to a ramp stretch of 2–5% is complex but can be resolved into four functionally different components. The behaviour displayed by the components ranges from pure viscous type (directly proportional to stretch velocity, ranging from 0.1 to 30 lengths s−1) to predominantly elastic type (insensitive to stretch velocity at 1–2 s time scale); simulations show two components of visco-elasticity with characteristically different relaxation times. The velocity-sensitive components (only) are enhanced by filament lattice compression (dextran – 500 kD) and by increased medium viscosity (dextran – 12 kD); also, the relaxation time of visco-elasticity is longer with increased medium viscosity. Amplitude of all the components and the relaxation time of visco-elasticity are increased at longer sarcomere length (range ∼2.5 – 3.0 μm). The study, and quantitative analyses, extend our previous work on intact muscle fibres and suggest that the velocity-sensitive tension components in intact sarcomere arise from interactions between sarcomeric filaments, filament segments and inter-filamentary medium; the two components of visco-elasticity arise from distinct regions of titin (connectin) molecules. [ABSTRACT FROM AUTHOR]

The effects of a ramp stretch (amplitude < 6% muscle fibre length ( L0), speed < 13 L0 s−1) on twitch tension and twitch tension re-development were examined in intact mammalian (rat) fast and slow muscle fibre bundles. The experiments were done in vitro at 20°C and at an initial sarcomere length of 2.68 μm. In both fibre types, a stretch applied during the rising phase of the twitch response (including the time of stimulation) increased the re-developed twitch tension (15–35%). A stretch applied before the stimulus had little or no effect on the twitch myogram in fast muscle fibres, but it increased the twitch tension (∼5%) in slow muscle fibres. A similar stretch had little or no effect on tetanic tension in either muscle fibre type. In general, the results indicate that the contractile-activation mechanism may be stretch sensitive and this is particularly pronounced in slow muscle fibres. Recorded at a high sampling rate and examined at an appropriate time scale, the transitory tension response to a stretch rose in at least two phases; an initial rapid tension rise to a break (break point tension, P1 a) followed by a slower tension rise (apparent P2 a) to a peak reached at the end of the stretch. Plotted against stretch velocity, P1 a tension increased in direct proportion to stretch velocity (viscous-like) whereas, P2 a tension (calculated as peak tension minus P1 a tension) increased with stretch velocity to a plateau (visco-elastic). Examined at the peak of a twitch, P1 a tension had a slope (viscosity coefficient) of 1.8 kNm−2 per L0 s−1 in fast fibres and 4.7 kNm−2 per L0 s−1 in slow muscle fibres. In the same preparations, P2 a tension had a relaxation time of 8 ms in the fast muscle fibres and 25 ms in the slow muscle fibres. The amplitudes of both tension components scaled with the instantaneous twitch tension in qualitatively the same way as the instantaneous fibre stiffness. These fast/slow fibre type differences probably reflect differences in their cross-bridge kinetics. [ABSTRACT FROM AUTHOR]

The sarcomere length change, within a 2 mm region, during end-held isometric contractions in intact rat fast and slow muscle fibre bundles was investigated at 20°C and an initial sarcomere length of 2.68 μm using He–Ne laser diffraction. In some experiments, the fibre segment displacement was monitored with markers (pieces of human hair) placed at regular intervals on the surface of the muscle fibre bundles. The sarcomere length changes, monitored near the proximal end of the bundle (transducer end), during tetanic contractions were similar to those previously reported in frog muscle fibres. Thus, throughout the tension plateau, sarcomere length remained constant (and shortened) but showed evidence of non-uniform sarcomere behaviour (further shortening) during the rapid tension relaxation phase. Such non-uniform behaviour was not seen during twitch contractions. During a twitch contraction, sarcomeres at the proximal end shortened rapidly at first and continued to shorten – or remained shortened – until the tension had relaxed to between 20–23% of its peak value before lengthening back to the original length. The maximum twitch sarcomere shortening (mean ± SEM) was 5.9 ± 0.2% ( n = 16) in fast and 5.4 ± 0.3% ( n = 14) in slow fibre bundles at 20°C; sarcomere shortening near body temperature (∼35°C) was greater, 8.8 ± 0.2% ( n = 7) in fast and 8.1 ± 0.2% ( n = 5) in slow fibre bundles. Increasing the initial sarcomere length of a preparation decreased the extent of sarcomere shortening and reducing the amount of sarcomere shortening, by sarcomere length clamping, markedly increased the peak twitch tension without significantly altering the twitch time course. When examined at different positions along muscle fibres, a sarcomere shortening was observed along much of the fibre length in most preparations. However, in about a third of the preparations some sarcomere lengthening was recorded in the distal end, but its amplitude was too small to accommodate the fibre shortening elsewhere. Complementary data were obtained using the surface marker technique. The displacement was largest and in opposite – but fibre shortening – direction in the markers placed ∼0.5–1.0 mm away from the two tendon attachments; the markers placed at or near the centre of the fibre bundle showed the least amount of displacement. The findings suggest that the compliant region, where lengthening occurs, is at fibre ends, i.e. near myotendinous junction. [ABSTRACT FROM AUTHOR]

Single intact muscle fibres isolated from the tibialis anterior muscle of the frog were exposed to hydrostatic pressures of 1–10 MPa, at 2–4°C and sarcomere length of 2.1–2.2 μm. The pressure was rapidly released (ca. 1 ms) to atmospheric level (0.1 MPa) during the plateau of a tetanic contraction (Po) and the resultant tension ( =force) transient examined. The pressure release induced tension transient consisted of an initial tension drop coincident with pressure release (ca. 4% Po per MPa, Phase 1), followed by a rapid recovery (Phase 2a) and a slower rise of tension (Phase 2b). Phase 1 was partly due to a length release at fibre ends (ca. 0.1 nm per half-sarcomere per MPa) induced by pressure-release effects on the steel chamber and fibre attachments, and partly due to ‘expansion’ upon pressure release within muscle fibre (ca. 0.2 nm per half-sarcomere per MPa), probably in the myofilaments and cross-bridges. The rate of tension recovery during phase 2a (ca. 600/s) was comparable to that of the quick tension recovery (T1-T2 transition) reported from moderately fast small length releases; the time course of Phase 2b (rate ca. 40/s) was similar to the late phase of tension rise in a tetanus, and hence compared with Phase 4 (T4) of a length release tension transient. Results are compared with the previously reported findings from analogous experiments on Ca2+-activated skinned (rabbit) muscle fibres. [ABSTRACT FROM AUTHOR]

Isometric tension responses to rapid temperature jumps (T-jumps) of 2–6°C were examined in skinned muscle fibre bundles isolated from papillary muscles of the rat heart. T-jumps were induced by an infra-red laser pulse (wave length 1.32 μm, pulse duration 0.2 ms) obtained from a Nd-YAG laser, which heated the fibres and bathing buffer solution in a 50 μl trough; the increased temperature by laser pulse was clamped at the high temperature by a Peltier system (see Ranatunga, 1996). In maximally Ca2+-activated (pCa ca. 4.5) fibres, the relationship between tension and temperature was non-linear, the increase of active tension with temperature being more pronounced at lower temperatures (below ca. 20°C). A T-jump at any temperature (range 3–35°C) induced an initial step decrease of tension of variable amplitude (Phase 1), probably due to thermal expansion, and it was followed by a tension transient which resulted in a net rise of tension above the pre-T-jump level. The rate of net rise of tension (Phase 2b or endothermic force generation) was 7–10/s at ca. 12°C and its Q10 was 6.3 (below 25°C). In cases where the step decrease of tension in Phase 1 was prominent, an initial quick tension recovery phase (Phase 2a, 70–100/s at 12°C) that did not contribute to a rise of tension above the pre-T-jump level, was also seen. This phase (Phase 2a) appeared to be similar to the quick tension recovery induced by a small length release and its rate increased with temperature with a Q10 of 1.8. In some cases where Phase 2a was present, a slower tension rise (Phase 3) was seen; its rate (ca. 5/s) was temperature-insensitive. The results show that the rate of endothermic force generation in cardiac fibres is clearly different from that of either fast-twitch or slow-twitch mammalian skeletal muscle fibres; implication of such fibre type-specific differences is discussed in relation to the difficulty in identifying the biochemical step underlying endothermic cross-bridge force generation. [ABSTRACT FROM AUTHOR]

Zymomonas mobilis CP4(pZB5) is a recombinant bacterium that can produce ethanol from both xylose and glucose. The ethanol-producing efficiency of this organism is substantially impeded by toxic substances present in pretreated hydrolyzates or solid biomass substrates. Acetic acid and furfural (a pentose degradation product) are highly toxic to this organism at levels envisioned for a pretreated-hardwood liquid hydrolyzate. In addition, lignin degradation products and 5-hydroxymethylfurfural (a hexose degradation product) have a moderately toxic effect on the organism. Of the compounds studied, organic acids and aldehydes were found to be more inhibitory than lignin acids or the one alkaloid studied. Acetone:water and methanol extracts of solid biomass samples from red oak, white oak, and yellow poplar are toxic to Zymomonas cell growth and ethanol production, with the extracts from white oak being the most toxic. [ABSTRACT FROM AUTHOR]

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