bluuebunny/crossref_metadata_2025 huggingface dataset:
Four‐week nutritional audit of preterm infants born <33 weeks gestation
Authors: McLeod Gemma , Sherriff Jill , Nathan Elizabeth , Hartmann Peter E , Simmer Karen
Published: December 2012

Aim

Preterm nutritional audits have previously been conducted using assumed milk composition. We audited protein and energy intakes in the first 28 days of preterm life using both assumed milk composition and milk analysis to assess their effect on weight gain and to determine if the recommended reasonable range of intakes were met.

Methods

Parenteral and enteral intakes and weight gain were recorded daily for infants (n = 63) born <33 weeks gestation, using assumed milk composition. Macronutrient composition was determined by milk analysis for a subset of infants (n = 36). Linear mixed models analysis was used to assess the influence of energy and protein intakes on weight gain.

Results

(Data median (range)): Infants (n = 63) gestation and birth weight were 30 (24–32) weeks and 1400 (540–2580) g, respectively. Macronutrient milk composition was variable: protein 16.6 (13.4–27.6) g/L, fat 46.1 (35.0–62.4) g/L, lactose 68.0 (50.9–74.8) g/L, energy 3074 (2631–3761) kJ/L. Intakes based on measured composition differed from assumed. Protein intake was significantly associated with weight gain. Compared to infants with longer gestations, those born <28 weeks gestation were fed lower volumes, were more reliant on parenteral nutrition, took an additional seven days to transition to fortified feeds and median weight gain velocity took a fortnight longer to reach targets.

Conclusion

Preterm milk composition is variable and routine fortification using assumed composition may result in inappropriate nutrition. Fortification regimens stratified by birth gestation may be necessary to achieve preterm nutrition and growth targets. Milk analysis is required for accurate nutritional audit.
Fatal and hospitalised childhood injuries in Fiji (TRIP Project‐3)
Authors: Naisaki Asilika , Wainiqolo Iris , Kafoa Berlin , Kool Bridget , Taoi Mabel , McCaig Eddie , Ameratunga Shanthi ,   TRIP Project Team
Published: December 2012

Aim

Although childhood injury rates in low‐ and middle‐income countries are known to be high, contemporary data on this topic from Pacific Island countries and territories are scant. We describe the epidemiology of childhood injuries resulting in death or hospital admission in Fiji using a population‐based registry.

Methods

A cross‐sectional analysis of the Fiji Injury Surveillance in Hospitals system investigated the characteristics associated with childhood injuries (<15 years) in Viti Levu, resulting in death or hospital admission (≥12 h) from October 2005 to September 2006.

Results

The 496 children meeting the study eligibility criteria corresponded to annual injury‐related hospitalisation and death rates of 265.4 and 15.3 per 100 000, respectively. Most (82%) deaths occurred prior to hospitalisation. The death and hospitalisation rates were highest among the <5‐ and 5‐ to 9‐year groups, respectively. Males and indigenous Fijian children were at increased risk of injury. The leading causes of injury death were road traffic injury (29%), choking (25%) and drowning (18%). Major causes of hospital admission were falls (48%), burns (13%), road traffic injury (11%) and being hit by a person or object (10%). Fractures and head injuries were the most common types of injury.

Conclusion

The findings support the need for a national strategy that builds capacity and mobilises resources to prevent childhood injuries in Fiji. Priority actions should include investment in technical support and research to identify local contextual and social determinants that inform the development and implementation of effective injury prevention interventions as a child health survival strategy.
Medical retrieval and needs of infants with bronchiolitis: An analysis by gestational age
Authors: Fleming Paul F , Richards Susie , Waterman Kelly , Davis Peter G , Kamlin C Omar F , Stewart Michael , Sokol Jenni
Published: December 2012

Aim

Viral bronchiolitis is the most common lower respiratory tract infection in children less than 12 months of age. Prematurity is an independent risk factor for disease severity. Many infected infants require hospitalisation and those living in regional centres frequently require transfer to metropolitan hospitals capable of providing assisted ventilation.

Method

We reviewed infants with bronchiolitis transported by the Victorian Newborn Emergency Transport Service between January 2003 and June 2007. We compared the clinical presentation and treatment required by infants born preterm with those of their term counterparts.

Results

Of the 192 infants transported, 92 were born preterm. Preterm infants were younger at time of transport (mean post‐menstrual age 41 weeks vs. 45 weeks) and were more likely to require invasive ventilation (60% vs. 32%, P < 0.001) and to receive a fluid bolus (47% vs. 34%, P = 0.04) when compared with infants who had been born at term. Apnoea, either as a presenting symptom or in combination with respiratory distress, was more common in the preterm group (70% vs. 36%, P < 0.001).

Conclusion

Higher illness severity should be anticipated in ex‐preterm infants who present with bronchiolitis. Preterm infants with bronchiolitis are more likely to require invasive ventilation and fluid resuscitation than term infants, suggesting the need for a lower threshold for referral and medical retrieval.
Virulence and Molecular Diversity of Venturia inaequalis in Commercial Apple Growing Regions in Kashmir
Authors: Padder Bilal Ahmad , Sofi Tariq Ahmad , Ahmad Mushtaq , Shah Mehraj‐Ul‐Din , Hamid Aflaq , Saleem Sehar , Ahanger Farooq Ahmad
Published: December 2012

Seventy‐one isolates of Venturia inaequalis collected from commercial apple growing areas of Kashmir were characterized on international differential apple hosts and analyzed by Random Amplified Polymorphic Microsatellites (RAMS), PCR–RFLP and sequencing of rDNA for elucidation of variability. Virulence analysis on a differential set categorized them into four pathogenic races, viz. (0), (1), (2) and (1,2) in the first time comprehensive molecular analysis of this in India and especially from Jammu and Kashmir, a north‐western Himalayan state of India. Race groups (0), (1), (2) and (1,2) contained isolates from diverse areas without specificity to any geographical zone or region. Cluster analysis of the RAMS and PCR–RFLP revealed a high genotypic diversity within V. inaequalis isolates. Three major clusters were obtained and the isolates could not be categorized on the basis of either their geographical distribution or the cultivar from which they were isolated. amova analysis of pathogen populations at regional or race level revealed high diversity within the populations. Pairwise FST comparisons between the populations revealed less genetic differentiation, thereby indicating existence of frequent gene flow in Kashmir. The 24 rDNA sequences of V. inaequalis showed high haplotype diversity of 0.938 and 0.40 nucleotide diversity. Again clustering at regional or race level detected greater part of variability within groups than among groups, thereby indicating high diversity in V. inaequalis populations in Kashmir valley.
Melatonin potentiates the antiproliferative and pro‐apoptotic effects of ursolic acid in colon cancer cells by modulating multiple signaling pathways
Authors: Wang Jingshu , Guo Wei , Chen Wangbing , Yu Wendan , Tian Yun , Fu Lingyi , Shi Dingbo , Tong Bing , Xiao Xiangsheng , Huang Wenlin , Deng Wuguo
Published: December 2012

Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is largely distributed in medical herbs and edible plants. Melatonin is an indoleamine compound produced in the pineal gland and also a plant‐derived product. Both UA and melatonin have been shown to inhibit cancer cell growth in numerous studies, but they have never been combined altogether as an anticolon cancer treatment. In this study, we investigated whether the association between UA and melatonin leads to an enhanced antiproliferative and pro‐apoptotic activities in colon cancer SW480 and LoVo cells. We found that combined treatment with UA and melatonin significantly enhanced inhibition of cell viability and migration, promoted changes in cell morphology and spreading, and increased induction of apoptosis, thereby potentiating the effects of UA alone in colon cancer cells. Moreover, we found that the enhanced effects of UA and melatonin combination are mediated through simultaneous modulation of cytochrome c/caspase, MMP9/COX‐2, and p300/NF‐κB signaling pathways. Combined treatment with UA and melatonin triggered the release of cytochrome c from the mitochondrial intermembrane space into the cytosol, induced cleavage of caspase and PARP proteins, enhanced inhibition of MMP9 and COX‐2 expression, promoted p300 and NF‐κB translocation from cell nuclei to cytoplasm, and abrogated NF‐κB binding and p300 recruitment to COX‐2 promoter in colon cancer cells. These results, therefore, demonstrated that melatonin potentiated the antiproliferative and pro‐apoptotic effects of UA in colon cancer cells by modulating multiple signaling pathways and suggest that such a combinational treatment might potentially become an effective way in colon cancer therapy.
Reproductive effort of Mastocarpus papillatus (Rhodophyta) along the California coast1
Authors: Krueger‐Hadfield Stacy A. , Kübler Janet E. , Dudgeon Steven R.
Published: December 2012

Species with sexual and asexual life cycles may exhibit intraspecific differences in reproductive effort. The spatial separation of sexual and asexual lineages, called geographic parthenogenesis, is common in plants, animals, and algae. Mastocarpus papillatus is a well‐documented case of geographic parthenogenesis in which sexuals dominate southern populations, asexuals dominate northern popula‐tions, whereas mixed populations occur throughout central California. We quantified abundances and reproductive effort of sexual and asexual fronds and tetrasporophytes at eight sites in California to test the hypotheses that (1) reduced sexual reproduction at higher latitudes and tidal heights explains the observed geographic parthenogenesis and (2) reproductive effort (spore production per blade area) declines with increasing latitude. Abundances of all phases varied site‐specifically. However, there was no geographic pattern of reproductive effort of fronds. Reproductive effort of fronds was greater in 2006 than in 2007 and correlated with sea surface temperatures. Sexual fronds exhibited greater reproductive effort than did asexual fronds and sexual reproductive effort was also inversely correlated with local upwelling index. Tetrasporophytes showed greater repro‐ductive effort in northern sites, but total supply of tetraspores per m2 was greatest in the middle of the sampling range where crusts were more abundant. There was no decline of reproductive effort at higher latitudes. Geographic patterns of fecundity of life stages do not explain geographic parthe‐nogenesis in M. papillatus. Site‐specific differences in viability among spores or established thalli of different life cycles may explain their respective geographic distributions, as the sexual and asexual life cycles responded differently to environmental variations.
DnaN clamp zones provide a platform for spatiotemporal coupling of mismatch detection to DNA replication
Authors: Lenhart Justin S. , Sharma Anushi , Hingorani Manju M. , Simmons Lyle A.
Published: December 2012

Mismatch repair (MMR) increases the fidelity of DNA replication by identifying and correcting replication errors. Processivity clamps are vital components of DNA replication and MMR, yet the mechanism and extent to which they participate in MMR remains unclear. We investigated the role of the Bacillus subtilis processivity clamp DnaN, and found that it serves as a platform for mismatch detection and coupling of repair to DNA replication. By visualizing functional MutS fluorescent fusions in vivo, we find that MutS forms foci independent of mismatch detection at sites of replication (i.e. the replisome). These MutS foci are directed to the replisome by DnaN clamp zones that aid mismatch detection by targeting the search to nascent DNA. Following mismatch detection, MutS disengages from the replisome, facilitating repair. We tested the functional importance of DnaN‐mediated mismatch detection for MMR, and found that it accounts for 90% of repair. This high dependence on DnaN can be bypassed by increasing MutS concentration within the cell, indicating a secondary mode of detection in vivo whereby MutS directly finds mismatches without associating with the replisome. Overall, our results provide new insight into the mechanism by which DnaN couples mismatch recognition to DNA replication in living cells.
Stigma among Iranian family caregivers of patients with Alzheimer's disease: A hermeneutic study
Authors: Navab Elham , Negarandeh Reza , Peyrovi Hamid , Navab Peyman
Published: December 2012

Although there is evidence of stigmatization of patients with Alzheimer's disease, few studies have evaluated stigma among family caregivers. This study was aimed at understanding the experiences of family caregivers of persons with Alzheimer's disease within Iran. We conducted a qualitative study using hermeneutic phenomenology. Semistructured in‐depth interviews with 10 Iranian family caregivers of persons with Alzheimer's were audiotaped and transcribed. The transcriptions were then analyzed using Van Manen's method. Family stigma emerged as one of the most important themes in this study. It consisted of two subthemes of “feeling of shame due to the unusual behaviors and speech of the patients” and “fear of judgments made by others.” An understanding of the experience of family stigma may lead to the development of supportive strategies to manage this problem among the caregivers. Educating families of patients about the disease plays a critical role in facilitating the process of caregiving. In addition, promoting public awareness about Alzheimer's disease can diminish stigma and prejudice toward patients and their caregivers. Educating caregivers on stigma management may also be an important factor in alleviating their stress.
Male‐specific DNA markers provide genetic evidence of an XY chromosome system, a recombination arrest and allow the tracing of paternal lineages in date palm
Authors: Cherif Emira , Zehdi Salwa , Castillo Karina , Chabrillange Nathalie , Abdoulkader Sabira , Pintaud Jean‐Christophe , Santoni Sylvain , Salhi‐Hannachi Amel , Glémin Sylvain , Aberlenc‐Bertossi Frédérique
Published: December 2012

Whether sex chromosomes are differentiated is an important aspect of our knowledge of dioecious plants, such as date palm (Phoenix dactylifera). In this crop plant, the female individuals produce dates, and are thus the more valuable sex. However, there is no way to identify the sex of date palm plants before reproductive age, and the sex‐determining mechanism is still unclear.

To identify sex‐linked microsatellite markers, we surveyed a set of 52 male and 55 female genotypes representing the geographical diversity of the species.

We found three genetically linked loci that are heterozygous only in males. Male‐specific alleles allowed us to identify the gender in 100% of individuals. These results confirm the existence of an XY chromosomal system with a nonrecombining XY‐like region in the date palm genome. The distribution of Y haplotypes in western and eastern haplogroups allowed us to trace two male ancestral paternal lineages that account for all known Y diversity in date palm.

The very low diversity associated with Y haplotypes is consistent with clonal paternal transmission of a nonrecombining male‐determining region. Our results establish the date palm as a biological model with one of the most ancient sex chromosomes in flowering plants.
Emerging Ethnic Identities and Inter‐Ethnic Conflict: The Guji–Burji Conflict in South Ethiopia
Authors: Debelo Asebe Regassa
Published: December 2012

The politics of ethnicity was formally institutionalised in Ethiopia in 1991 with the introduction of ethnic federalism. This study deals with emerging ethnic identities and the dynamics of the inter‐ethnic relationship between the Guji and Burji peoples in south Ethiopia. The article argues that, following the enunciation of ethnicity as a leading political order in 1991, identities have been articulated in such a way that past historical incidents and memories have been reactivated and old labels have been redefined by ethnic entrepreneurs for various motives. This promotes (re)construction of ethnic identities and inter‐group polarisation. In the Guji–Burji case, it is this fragile relationship that is easily changed into inter‐ethnic conflict as a result of competing interests over resources. The article concludes that while the cause of the current Guji–Burji conflict is primarily economic in nature, it took on an ethnic dimension within the context of politicised ethnic identities that hardened group boundaries. Synchronising past relationships – both conflicting and harmonious – with the contemporary scenario, the article tries to shed some light on the dynamics of the Guji–Burji relationship, focusing particularly on the post‐1991 political order in Ethiopia and its local implications.
Modulation of Ets‐1 Expression in B Lymphocytes is Dependent on the Antigen Receptor–mediated Activation Signals and Cell Cycle Status
Authors: Raghunandan R. , Frissora F. W. , Muthusamy N.
Published: December 2012

In this report, we tested the hypothesis that Ets‐1 transcription factor is modulated at the mRNA level during B cell antigen receptor (BCR)‐induced cell‐signalling events. Quiescent B cells express high levels of Ets‐1 mRNA. Stimulation through the BCR results in time‐dependent inhibition of Ets‐1 mRNA expression in primary splenic B cells with maximal inhibition observed by 16‐h post‐stimulation. Inhibition of Ets‐1 expression is specific to antigen receptor but not CD40‐mediated activation. Antigen receptor–induced inhibition of Ets‐1 mRNA can be mimicked by phorbol myristate acetate (PMA) and/or ionomycin. PMA but not ionomycin‐induced inhibition of Ets‐1 expression is rescued by the inhibitors of protein kinase C and MEK. Extended time‐course analysis revealed a time‐dependent cyclical pattern in the re‐expression of Ets‐1 mRNA. While resting cells revealed maximal Ets‐1 mRNA expression, activation events that induced exit from G0/G1 or cells blocked in early S phase exhibited decreased Ets‐1 mRNA levels. Interestingly, cells arrested at late G2 or M phase of the cell cycle failed to down modulate Ets‐1 mRNA expression. Overexpression of Ets‐1 in 70Z/3 B cell line caused abnormal accumulation of cells in S phase associated with increased cyclin A expression. Consistent with a requirement for Ets‐1 in BCR‐induced cell cycle entry, splenic B cells from mice deficient in Ets‐1 showed defective antigen receptor–induced DNA synthesis and S phase entry. These results suggest a critical role for Ets‐1 regulation during B cell activation and cell cycle entry.
Cytomegalovirus‐Specific CD4 and CD8 T Cell Responses in Infants and Children
Authors: Lidehäll A. K. , Engman M.‐L. , Sund F. , Malm G. , Lewensohn‐Fuchs I. , Ewald U. , Tötterman T. H. , Karltorp E. , Korsgren O. , Eriksson B.‐M.
Published: December 2012

Congenital cytomegalovirus (CMV) infection is the most common congenital infection causing childhood morbidity. The pathogenetic mechanisms behind long‐term sequelae are unclear, but long‐standing viremia as a consequence of the inability to convert the virus to a latent state has been suggested to be involved. Whereas primary CMV infection in adults is typically rapidly controlled by the immune system, children have been shown to excrete virus for years. Here, we compare T cell responses in children with congenital CMV infection, children with postnatal CMV infection and adults with symptomatic primary CMV infection. The study groups included 24 children with congenital CMV infection, 19 children with postnatal CMV infection and eight adults with primary CMV infection. Among the infants with congenital CMV infection, 13 were symptomatic. T cell responses were determined by analysis of interferon gamma production after stimulation with CMV antigen. Our results show that whereas adults display high CMV‐specific CD4 T cell responses in the initial phase of the infection, children younger than 2 years have low or undetectable responses that appear to increase with time. There were no differences between groups with regard to CD8 T cell function. In conclusion, inadequate CD 4 T cell function seems to be involved in the failure to get immune control of the CMV infection in children younger than 2 years of age with congenital as well as postnatal CMV infection.
Localised Agro‐Food Systems and Geographical Indications in the Face of Globalisation: The Case of Queso Chontaleño
Authors: Mancini Maria Cecilia
Published: December 2012

This study analyses a localised agro‐food system producing Queso Chontaleño (QC) cheese in the Chontales Department in Nicaragua and the first effects of the Geographical Indication (GI) scheme which alters the power relations between the actors of the cheese‐dairy sector within the framework of global dynamics. The first part focuses on systèmes agro‐alimentaires localisés (SYAL), or localised agro‐food systems, and it provides the theoretical background to the case study. The second part analyses the QC SYAL and its territorial and institutional context. It is found that GI introduces new competitive pressures that reinforce local elites at the expense of traditional QC actors and that the weak involvement of the State may prevent GIs from enhancing the development of territorialised agro‐food systems. The conclusion is a recommendation to EU policymakers that promotion of GIs at the level of the WTO be accompanied by measures that can ensure stricter national legislations on GIs to protect local resources.
Characterization of a new HLA‐C*04 allele, C*04:112
Authors: Ferriola D. , Heron S. , Lind C. , Monos D. S.
Published: December 2012

HLA‐C*04:112 differs from HLA‐C*04:01:01:01 by one nucleotide at position 270 resulting in an amino acid change, Lysine to Asparagine, at codon 66 of exon 2.
Rapid diagnosis of retina and optic nerve abnormalities in canine patients with and without cataracts using chromatic pupil light reflex testing
Authors: Grozdanic Sinisa D. , Kecova Helga , Lazic Tatjana
Published: December 2012

Objective To develop fast and reliable testing routines for diagnosing retina and optic nerve diseases in canine cataract patients based on chromatic properties of the pupillary light reflex response.

Procedures Seventy‐seven canine patients with a history of cataract and decreased vision (43 patients with cataracts and no evidence of retina or optic nerve disease, 21 patients with cataracts and retinal degeneration [RD], 13 patients with cataracts and retinal detachment [RDT]), 11 canine patients with optic neuritis (ON) and 23 healthy dogs were examined using chromatic pupillary light reflex (cPLR) analysis with red and blue light and electroretinography.

Results Electroretinography analysis showed statistically significant deficits in a‐ and b‐wave amplitudes in dogs with cataracts and RD, or cataracts and RDT, when compared to dogs with cataracts without evidence of retinal abnormalities. Evaluation of b‐wave amplitudes showed that presence of 78.5‐μV (or lower) amplitudes had high sensitivity of 100% (95% CI: 87.2–100%) and high specificity of 96.7% (95% CI: 88.4–100%) in RD and RDT. Evaluation of cPLR responses using red light showed that presence of the pupil end constriction diameter of 5.5 mm (or higher) had moderately high sensitivity of 76.5% (95% CI: 50.1–93.2%) and high specificity of 100% (95% CI: 91.2–100%) in detecting RD and RDT. Optic neuritis patients had absent cPLR responses, regardless of the visual status.

Conclusions and Clinical Relevance Chromatic evaluation of the pupillary light reflex is a rapid and accurate test for diagnosing retina and optic nerve diseases in canine patients.
Corneal stromal abscessation in two horses treated with intracorneal and subconjunctival injection of 1% voriconazole solution
Authors: Tsujita Hiroki , Plummer Caryn E.
Published: December 2012

Objective

To describe and evaluate intrastromal and subconjunctival injection of voriconazole for the therapy of deep corneal stromal abscess (DSA) in horses.

Animal studied

A retrospective clinical study describing the indications for intrastromal and subconjunctival voriconazole injection and the outcomes of this procedure in two eyes of two horses.

Procedure

The two horses in this study failed to respond to medical therapy. Treatment with intracorneal and subconjunctival administration of 1% voriconazole was performed in this study.

Results

Treatment with intracorneal and subconjunctival administration of 1% voriconazole was successful in resolving the corneal stromal abscess and the secondary uveitis. Immediate complications from the intracorneal injection occurred, which included corneal stromal lamellar fracture (2/2) and conjunctival hyperemia/chemosis (2/2). Also subconjunctival hemorrhage (1/2) due to the subconjuctival voriconazole injection occurred (2/2). Chronic complications of the intracorneal injection included mild‐moderate corneal stromal fibrosis (2/2).

Conclusions

This procedure may be an effective technique to treat refractory or relapsingDSAin horses. Intracorneal and subconjunctival voriconazole administration results in a visual and cosmetically acceptable globe. In equineDSAcases, the advantages of this technique compared with other medical and surgical approaches to this disease include shortened anesthesia times, minimal resultant scarring and shorter healing times, and lower cost of therapy.
New vistas on astroglia in convulsive and non‐convulsive epilepsy highlight novel astrocytic targets for treatment
Authors: Crunelli Vincenzo , Carmignoto Giorgio
Published: December 2012

Abstract  Our current knowledge of the role of astrocytes in health and disease states supports the view that many physiological brain functions and neurological diseases are finely tuned, and in certain cases fully determined, by the continuous cross‐talk between astrocytes and neurons. This novel way of interpreting brain activity as a dynamic and reciprocal interplay between astrocytic and neuronal networks has also influenced our understanding of epilepsy, not only forcing a reinterpretation of old findings, but also being a catalyst for novel experimentation. In this review, we summarize some of the recent studies that highlight these novel distinct contributions of astrocytes to the expression of convulsive and non‐convulsive epileptiform discharges and seizures. The emerging picture suggests a general framework based on bilateral signalling between astrocytes and neurons for a fuller understanding of epileptogenic and epileptic mechanisms in the brain network. Astrocytes potentially represent targets for the development of those novel chemical entities with improved efficacy for the treatment of convulsive and non‐convulsive epilepsy that expert groups have recognized as one of the key priorities for the management of epilepsy.
Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals
Authors: Fisher James P. , Hartwich Doreen , Seifert Thomas , Olesen Niels D. , McNulty Clare L. , Nielsen Henning B. , van Lieshout Johannes J. , Secher Niels H.
Published: December 2012

Key points

The influence of normative ageing on cerebral perfusion, oxygenation and metabolism during exercise is not well known.

This study assessed cerebral perfusion and concentration differences for oxygen, glucose and lactate across the brain, in young and elderly individuals at rest and during incremental exercise to exhaustion.

We observed that during submaximal exercise (at matched relative intensities) and during maximal exercise, cerebral perfusion was reduced in older individuals compared with young individuals, while the cerebral metabolic rate for oxygen and uptake of glucose and lactate were similar.

The results indicate that the age‐related reduction in cerebral perfusion during exercise does not affect brain uptake of lactate and glucose.

Abstract  We evaluated cerebral perfusion, oxygenation and metabolism in 11 young (22 ± 1 years) and nine older (66 ± 2 years) individuals at rest and during cycling exercise at low (25%Wmax), moderate (50%Wmax), high (75%Wmax) and exhaustive (100%Wmax) workloads. Mean middle cerebral artery blood velocity (MCA Vmean), mean arterial pressure (MAP), cardiac output (CO) and partial pressure of arterial carbon dioxide () were measured. Blood samples were obtained from the right internal jugular vein and brachial artery to determine concentration differences for oxygen (O2), glucose and lactate across the brain. The molar ratio between cerebral uptake of O2 versus carbohydrate (O2–carbohydrate index; O2/[glucose +1/2 lactate]; OCI), the cerebral metabolic rate of O2 (CMRO2) and changes in mitochondrial O2 tension () were calculated. 100%Wmax was ∼33% lower in the older group. Exercise increased MAP and CO in both groups (P < 0.05 vs. rest), but at each intensity MAP was higher and CO lower in the older group (P < 0.05). MCA Vmean, and cerebral vascular conductance index (MCA Vmean/MAP) were lower in the older group at each exercise intensity (P < 0.05). In contrast, young and older individuals exhibited similar increases in CMRO2 (by ∼30 μmol (100 g−1) min−1), and decreases in OCI (by ∼1.5) and (by ∼10 mmHg) during exercise at ≥75%Wmax. Thus, despite the older group having reduced cerebral perfusion and maximal exercise capacity, cerebral oxygenation and uptake of lactate and glucose are similar during exercise in young and older individuals.
Role of nocturnal rostral fluid shift in the pathogenesis of obstructive and central sleep apnoea
Authors: White Laura H. , Bradley T. Douglas
Published: December 2012

Abstract  Obstructive sleep apnoea (OSA) is common in the general population and increases the risk of motor vehicle accidents due to hypersomnolence from sleep disruption, and risk of cardiovascular diseases owing to repetitive hypoxia, sympathetic nervous system activation, and systemic inflammation. In contrast, central sleep apnoea (CSA) is rare in the general population. Although their pathogenesis is multifactorial, the prevalence of both OSA and CSA is increased in patients with fluid retaining states, especially heart failure, where they are associated with increased mortality risk. This observation suggests that fluid retention may contribute to the pathogenesis of both OSA and CSA. According to this hypothesis, during the day fluid accumulates in the intravascular and interstitial spaces of the legs due to gravity, and upon lying down at night redistributes rostrally, again owing to gravity. Some of this fluid may accumulate in the neck, increasing tissue pressure and causing the upper airway to narrow, thereby increasing its collapsibility and predisposing to OSA. In heart failure patients, with increased rostral fluid shift, fluid may additionally accumulate in the lungs, provoking hyperventilation and hypocapnia, driving below the apnoea threshold, leading to CSA. This review article will explore mechanisms by which overnight rostral fluid shift, and its prevention, can contribute to the pathogenesis and therapy of sleep apnoea.
Different NMDA receptor subtypes mediate induction of long‐term potentiation and two forms of short‐term potentiation at CA1 synapses in rat hippocampus in vitro
Authors: Volianskis Arturas , Bannister Neil , Collett Valerie J. , Irvine Mark W. , Monaghan Daniel T. , Fitzjohn Stephen M. , Jensen Morten S. , Jane David E. , Collingridge Graham L.
Published: December 2012

Key points

N‐Methyl‐d‐aspartate receptor (NMDAR)‐dependent potentiation of synaptic transmission is widely accepted as a cellular model of learning and memory.

It is most often studied in the CA1 area of rat hippocampal slices where it comprises a decremental and a sustained phase, which are commonly referred to as short‐term potentiation (STP) and long‐term potentiation (LTP), respectively.

In this study we show for the first time that STP and LTP are triggered by the activation of different classes of NMDARs and that STP itself comprises two pharmacologically and kinetically distinct components.

We suggest that the mechanistic separation of STP and LTP is likely to have important functional implications in that these two forms of synaptic plasticity can subserve unique physiological functions in a behaving animal.

Abstract  Potentiation at synapses between CA3 and the CA1 pyramidal neurons comprises both transient and sustained phases, commonly referred to as short‐term potentiation (STP or transient LTP) and long‐term potentiation (LTP), respectively. Here, we utilized four subtype‐selective N‐methyl‐d‐aspartate receptor (NMDAR) antagonists to investigate whether the induction of STP and LTP is dependent on the activation of different NMDAR subtypes. We find that the induction of LTP involves the activation of NMDARs containing both the GluN2A and the GluN2B subunits. Surprisingly, however, we find that STP can be separated into two components, the major form of which involves activation of NMDARs containing both GluN2B and GluN2D subunits. These data demonstrate that synaptic potentiation at CA1 synapses is more complex than is commonly thought, an observation that has major implications for understanding the role of NMDARs in cognition.
Atomic layer deposition onto carbon fiber: From single layer deposition via multilayer structure to metal oxide microtubes
Authors: Knohl Stefan , Kumar Roy Amit , Goedel Werner A. , Schulze Steffen , Hietschold Michael
Published: December 2012

Layers of alumina, titania and double layers of alumina/titania (and reverse) were deposited onto bundles of carbon fibers in an atomic layer deposition process. Scanning electron microscopy (SEM) images of the coated carbon fibers revealed that each fiber of a bundle was coated homogenously and separately and that no bridges were formed between the fibers. Transmission electron microscopy and SEM images showed that the coating was conformal, uniform, had a good adhesion to the fiber surface and that the morphology of the coating surface was similar to that of fiber surface. In case of double layers, the average deposition rate of coatings did not depend on the sequence of layer deposition. After coating, the carbon fibers were selectively removed by thermal oxidation in air at temperatures of 550 °C and 900 °C, leading to metal oxide microtubes.
Reindeer Diode
Authors: Mattila Jukka O.
Published: December 2012

In Finnish Lapland, like in other Northern European regions by the Arctic Sea, aboriginal Sami people still base much of their daily income on reindeer. Earlier the Sami people followed their reindeer herds more or less all the year round, in nomadic fashion. Moving to fixed dwellings has created a problem in herding and guarding the property of the moving wild packs of hundreds or thousands of reindeer, which Sami families usually possess. Already for decades the mobility provided by Ski-Doos—along with herding dogs—has helped with the job. However, the era of limitless wilderness in reindeer herding is over. Nowadays hundreds of kilometers of reindeer fence separate Sami herding districts from each other.
Demonstrating Sound Wave Propagation with Candle Flame and Loudspeaker
Authors: Hrepic Zdeslav , Nettles Corey , Bonilla Chelsea
Published: December 2012

The motion of a candle flame in front of a loudspeaker has been suggested as a productive demonstration of the longitudinal wave nature of sound.1 The demonstration has been used also as a research tool to investigate students' understanding about sound.2–4 The underpinning of both applications is the expectation of a horizontal, back-and-forth vibration of the flame around its upright position. Unlike experts, who regularly anticipate this outcome, students with no previous formal knowledge typically anticipate that the flame will lean away from the speaker.
Modeling the Dynamics of Gel Electrophorresis in the High School Classroom
Authors: Saucedo Skyler R.
Published: December 2012

Gel electrophoresis, used by geneticists and forensic experts alike, is an immensely popular technique that utilizes an electric field to separate molecules and proteins by size and charge. At the microscopic level, a dye or complex protein like DNA is passed through agarose, a gelatinous three-dimensional matrix of pores and nano-sized tunnels. When forced through a maze of holes, the molecule unravels, forming a long chain, slithering through the field of pores in a process colloquially coined “reputation.”1 As a result, the smaller molecules travel farther through the gel when compared to molecules of larger molecular weight. This highly effective “molecular sieve” provides consistent data and allows scientists to compare similar sequences of DNA base pairs in a routine fashion.2 When performed at the high school level, gel electrophoresis provides students the opportunity to learn about a contemporary lab technique of great scientific relevance. Doing real science certainly excites students and motivates them to learn more.
The 2013 Nationwide Survey of High School Physics Teachers
Authors: White Susan
Published: December 2012

The data we report on in this column come from the Nationwide Survey of High School Physics Teachers. Since 1987, the American Institute of Physics (AIP) and the American Association of Physics Teachers (AAPT) have sponsored the High School Teacher Survey. Prior to our initial study, much of the previous literature focusing on high school physics employed anecdotal evidence or qualitative surveys for curriculum reviews or explorations of teachers' experiences and pedagogical techniques. As a direct response to this dearth of data, the Nationwide Survey of High School Physics Teachers was initiated in 1986–87 to answer questions about the number of teachers teaching physics, the educational background of these teachers, the number of students enrolled in physics, the variety of physics classes being offered, the demographics of the students and teachers, the textbooks being used, and the number of high schools offering physics regularly. Since the beginning of this study, we have surveyed both public and private high schools in the United States. The results of our study provide the definitive data about physics in U.S. high schools. The initial survey was conducted during the 1986–87 school year. The second was completed during 1989–90. Beginning with the 1992–93 survey, we have conducted the survey every four years. The 2012–13 survey will be the eighth in the series. Thus, we have a rich history of physics teaching in U.S. high schools.
Mini-“Bell in a Bell Jar”
Authors: Wei Zhang , Jiali Hou , Wenfang Yang
Published: December 2012

A number of versions of the well-known “bell-in-a-bell-jar” demonstration have been discussed in this journal.1–3 The basic idea is that when a sound source is placed inside an air-tight container, the volume of the sound that's heard decreases dramatically when the container is evacuated. This phenomenon is primarily due to the mismatch that is created between the sound transducer and the surrounding medium.4,5 Here we describe a simple small-scale version of this demonstration, one that may be added to the growing list of examples of how a simple syringe may be used as a tool in physics teaching.6–8
Quantitative Screening for Anticestode Drugs Based on Changes in Baseline Enzyme Secretion by Taenia crassiceps
Authors: Mahanty Siddhartha , Madrid Elise M. , Nash Theodore E.
Published: December 2012

Neurocysticercosis (NCC), an infection of the brain with the larval stage of the
Taenia solium
tapeworm, is responsible for an estimated one-third of adult-onset epilepsy cases in regions of the world where it is endemic. Currently, anthelmintic drugs used for treatment of NCC are only partially effective, and there is, therefore, a pressing need for new therapeutic agents. Discovery of new anthelmintics with activity against
T. solium
has been limited by the lack of suitable sensitive assays that allow high-throughput screening. Using an
in vitro
culture system with
Taenia crassiceps
metacestodes, we demonstrate that changes in secretion of parasite-associated alkaline phosphatase (AP) and phosphoglucose isomerase (PGI) can be used to detect and quantify anthelmintic effects of praziquantel (PZQ), a drug with activity against
T. solium
. We applied two enzyme release assays to screen for anti-
T. crassiceps
activity in nonconventional antiparasitic drugs and demonstrate that nitazoxanide and artesunate induced release of both AP and PGI in differing time- and dose-related patterns. Furthermore, imatinib, a tyrosine kinase inhibitor previously reported to have parasiticidal activity against
Schistosoma mansoni
, also induced release of both AP and PGI in a dose-dependent manner, similar in pattern to that observed with the other anthelmintics. We also evaluated release of ATP into cyst supernatants as an indicator of drug effects but did not see any differences between treated and untreated cysts. These data provide the basis for rapid and quantitative screening assays for testing for anthelmintic activity in candidate anticestode agents.
In Vitro
Activity of a New Oral Glucan Synthase Inhibitor (MK-3118) Tested against Aspergillus spp. by CLSI and EUCAST Broth Microdilution Methods
Authors: Pfaller Michael A. , Messer Shawn A. , Motyl Mary R. , Jones Ronald N. , Castanheira Mariana
Published: December 2012

MK-3118, a glucan synthase inhibitor derived from enfumafungin, and comparator agents were tested against 71
Aspergillus
spp., including itraconazole-resistant strains (MIC, ≥4 μg/ml), using CLSI and EUCAST reference broth microdilution methods. The CLSI 90% minimum effective concentration (MEC
90
)/MIC
90
values (μg/ml) for MK-3118, amphotericin B, and caspofungin, respectively, were as follows: 0.12, 2, and 0.03 for
Aspergillus flavus
species complex (SC); 0.25, 2, and 0.06 for
Aspergillus fumigatus
SC; 0.12, 2, and 0.06 for
Aspergillus terreus
SC; and 0.06, 1, and 0.03 for
Aspergillus niger
SC. Essential agreement between the values found by CLSI and EUCAST (±2 log
2
dilution steps) was 94.3%. MK-3118 was determined to be a potent agent regardless of the
in vitro
method applied, with excellent activity against contemporary wild-type and itraconazole-resistant strains of
Aspergillus
spp.
Exposure of Salmonella enterica Serovar Typhimurium to a Protective Monoclonal IgA Triggers Exopolysaccharide Production via a Diguanylate Cyclase-Dependent Pathway
Authors: Amarasinghe Jayaleka J. , D'Hondt Rebecca E. , Waters Christopher M. , Mantis Nicholas J.
Published: December 2012

Sal4 is a monoclonal polymeric IgA antibody directed against the O antigen (O-Ag) of
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium), which is sufficient to protect mice against intestinal infections from
S
. Typhimurium. We recently reported that the exposure of
S
. Typhimurium to Sal4 results in the immediate loss of flagellum-based motility, in alterations to the outer membrane (OM) integrity, and in the concomitant appearance of a mucoid phenotype that is reminiscent of cells in the earliest stages of biofilm formation. We demonstrate here that prolonged (>4 h) exposure of
S
. Typhimurium to Sal4 at 37°C (but not at ambient temperature [25°C]) results in measurable exopolysaccharide (EPS) accumulation and biofilm formation on both borosilicate glass surfaces and polystyrene microtiter plates. The polysaccharide produced by
S
. Typhimurium in response to Sal4 contains cellulose, in addition to O-Ag capsule and colanic acid. EPS production was dependent on YeaJ, a proposed inner membrane-localized diguanylate cyclase (DGC) and a known regulator of cellulose biosynthesis. An
S
. Typhimurium Δ
yeaJ
strain was unable to produce cellulose or form a biofilm in response to Sal4. Conversely, the overexpression of
yeaJ
in
S
. Typhimurium enhanced Sal4-induced biofilm formation and resulted in increased intracellular levels of cyclic dimeric guanosine monophosphate (c-di-GMP) compared to that of a wild-type control; this strongly suggests that YeaJ is indeed a functional DGC. Based on these data, we speculate that Sal4, by virtue of its ability to associate with the O-Ag and to induce OM stress, renders
S
. Typhimurium avirulent by triggering a c-di-GMP-dependent signaling pathway via YeaJ that leads to the suppression of bacterial motility while simultaneously stimulating EPS production.
Helicobacter pylori Stores Nickel To Aid Its Host Colonization
Authors: Benoit Stéphane L. , Miller Erica F. , Maier Robert J.
Published: December 2012

The transition metal nickel (Ni) is critical for the pathogenicity of
Helicobacter pylori
. Indeed the element is a required component of two enzymes, hydrogenase and urease, that have been shown to be important for
in vivo
colonization of the host gastric mucosa. Urease accounts for up to 10% of the total cellular
H. pylori
protein content, and therefore the bacterial Ni demand is very high.
H. pylori
possess two small and abundant histidine-rich, Ni-binding proteins, Hpn and Hpn-like, whose physiological role in the host have not been investigated. In this study, special husbandry conditions were used to control Ni levels in the host (mouse), including the use of Ni-free versus Ni-supplemented food. The efficacy of each diet was confirmed by measuring the Ni concentrations in sera of mice fed with either diet. Colonization levels (based on rank tests) of the
Δhpn Δhpn
-like double mutants isolated from the mice provided Ni-deficient chow were statistically lower than those for mice given Ni in their diet. In contrast,
H. pylori
wild-type colonization levels were similar in both host groups (e.g., regardless of Ni levels). Our results indicate that the gastric pathogen
H. pylori
can utilize stored Ni via defined histidine-rich proteins to aid colonization of the host.
Activation of the Nlrp1b Inflammasome by Reduction of Cytosolic ATP
Authors: Liao Kuo-Chieh , Mogridge Jeremy
Published: December 2012

The efficacy of the innate immune system depends on its ability to mount an appropriate response to diverse infections and damaging agents. Key components of this system are pattern recognition receptors that detect pathogen-associated and damage-associated molecular patterns (PAMPs and DAMPs). Nlrp1b is a pattern recognition receptor that forms a caspase-1 activation platform, known as an inflammasome, upon sensing the proteolytic activity of anthrax lethal toxin. The activation of caspase-1 leads to the release of proinflammatory cytokines that aid in the clearance of the anthrax infection. Here, we demonstrate that Nlrp1b also becomes activated in cells that are subjected to energy stress caused by metabolic inhibitors or by nutrient deprivation. Glucose starvation and hypoxia were used to correlate the level of cytosolic ATP to the degree of inflammasome activation. Because lowering the ratio of cytosolic ATP to AMP activates the main cellular energy sensor, AMP-activated protein kinase (AMPK), we assessed whether AMPK promoted inflammasome activity by using a combination of small interfering RNA (siRNA) and transfection of a dominant negative AMPK subunit. We found that AMPK promoted inflammasome activity, but activation of AMPK in the absence of ATP depletion was not sufficient for caspase-1-mediated pro-interleukin 1β (pro-IL-1β) processing. Finally, we found that mutation of the ATP-binding motif of Nlrp1b caused constitutive activation, suggesting that ATP might inhibit the Nlrp1b inflammasome instead of being required for its assembly.