bluuebunny/crossref_metadata_2025_split huggingface dataset:
Living as a family in the midst of chronic illness
Authors: Årestedt Liselott , Persson Carina , Benzein Eva 
Published: January 2013

Aims and objectivesThe aim of the study was to illuminate the meaning of lived experience of living as a family in the midst of chronic illness.BackgroundChronic illness implies a change for both the individual and the family. In this changed situation, all family members seem to benefit from sharing experiences and receiving support. Current research highlights the individual patient's or family member's perspectives on chronic illness, but family systems nursing (FSN) studies are warranted.DesignA qualitative design with a FSN approach was chosen.MethodRepeated qualitative narrative interviews with seven families living with chronic illness were performed. A phenomenological hermeneutic analysis, inspired by Ricoeur, was used to interpret the data.ResultsThe phenomenon can be described as an ongoing movement towards well‐being. The results included two themes and five sub‐themes. The first theme was ‘Co‐creating a context for living with illness’ with the subthemes; ‘learning to live with the expressions of illness’ and ‘communicating the illness within and outside the family’. The second theme was ‘Co‐creating alternative ways for everyday life’ with the subthemes; ‘adapting to a new life rhythm’, ‘altering relationships’ and ‘changing roles and tasks in the family’.ConclusionsLiving as a family in the midst of chronic illness can be described as an ongoing process where the family members co‐create a context for living with illness. They also co‐create a context for alternative ways of everyday life.Relevance to clinical practiceKnowledge about lived experience of living as a family in the midst of chronic illness can help nurses to adopt a FSN care perspective. This can increase the chances of taking advantage of the ways family members manage situations together, as well as highlight resources within the family.
Identification of a cis‐element that mediates multiple pathways of the endoplasmic reticulum stress response in rice
Authors: Hayashi Shimpei , Takahashi Hideyuki , Wakasa Yuhya , Kawakatsu Taiji , Takaiwa Fumio 
Published: January 2013

SummaryThe accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress. Intracellular signalling pathways are activated to alleviate the stress. The ER stress sensor IRE1 induces the active form of key transcription factors, such as XBP1 in mammals and bZIP50 in Oryza sativa (rice), by mediating the unconventional splicing of their mRNAs. Although the characterization of cis‐elements that are recognized by these transcription factors is essential for understanding ER stress responses, such cis‐elements remain unidentified in plants. Here, a cis‐element named pUPRE–II was identified from promoters of bZIP50‐dependent genes using chromatin immunoprecipitation assays and electrophoretic mobility shift assays. The sequence of pUPRE–II (e.g. 5′–GATGACGCGTAC–3′ in the OsSAR1 promoter) was found to be flexible and not identical with that of mUPRE, a cis‐element that preferentially interacts with mammalian XBP1. Unexpectedly, the transcription factor bZIP60, another ER stress sensor in rice, and a counterpart of mammalian ATF6, also showed strong binding affinity for pUPRE–II without assistance from co‐factors. Reporter assays indicated that pUPRE–II significantly contributes to gene expression mediated by bZIP50 or bZIP60 in rice. Although both bZIP50 and bZIP60 bound to pUPRE–II, these transcription factors showed distinct requirements for transcriptional activation. This study provides a missing link between ER stress sensors and stress‐responsive genes in rice. Furthermore, the characteristics of pUPRE–II highlight the uniqueness of ER stress‐responsive transcription in plants.
Serotonergic control of Purkinje cell maturation and climbing fibre elimination by 5‐HT3 receptors in the juvenile mouse cerebellum
Authors: Oostland Marlies , Buijink M. Renate , van Hooft Johannes A. 
Published: January 2013

Key points
Serotonin 3 (5‐HT3) receptors are expressed by excitatory granule cells in the cerebellum during early postnatal development.
Here we show a novel role for serotonin in the regulation of cerebellar postnatal development via 5‐HT3 receptors.
Using 5‐HT3A receptor knockout mice we show that 5‐HT3 receptors expressed by granule cells, via the glycoprotein reelin, regulate the morphological maturation of Purkinje cells.
The 5‐HT3A receptor knockout mice show abnormal physiological maturation of Purkinje cells and impaired short‐term plasticity at the parallel fibre–Purkinje cell synapse, resulting in delayed climbing fibre elimination.
With these results, we provide a better understanding of the role of serotonin in the developing brain, the control it has on the postnatal maturation of the cerebellum, and the cerebellum as a highly adaptive system during early postnatal development.
Abstract  Functional serotonin 3 (5‐HT3) receptors are transiently expressed by cerebellar granule cells during early postnatal development, where they modulate short‐term synaptic plasticity at the parallel fibre–Purkinje cell synapse. Here, we show that serotonin controls maturation of Purkinje cells in the mouse cerebellum. The 5‐HT3 receptors regulate morphological maturation of Purkinje cells during early postnatal development, and this effect is mediated by the glycoprotein reelin. Using whole‐cell patch‐clamp recordings we also investigated physiological development of Purkinje cells in 5‐HT3A receptor knockout mice during early postnatal development, and found abnormal physiological maturation, characterized by a more depolarized resting membrane potential, an increased input resistance and the ability to fire action potentials upon injection of a depolarizing current at an earlier age. Furthermore, short‐term synaptic plasticity was impaired at both the parallel fibre–Purkinje cell and the climbing fibre–Purkinje cell synapses, and both the amplitude and the frequency of spontaneous miniature events recorded from Purkinje cells were increased. The expedited morphological and physiological maturation affects the whole cerebellar cortical network, as indicated by delayed climbing fibre elimination in 5‐HT3A receptor knockout mice. There was no difference between wild‐type and 5‐HT3A receptor knockout mice in any of the morphological or physiological properties described above at later ages, indicating a specific time window during which serotonin regulates postnatal development of the cerebellum via 5‐HT3 receptors expressed by granule cells.
Hyperpolarisation‐activated cyclic nucleotide‐gated channels regulate the spontaneous firing rate of olfactory receptor neurons and affect glomerular formation in mice
Authors: Nakashima Noriyuki , Ishii Takahiro M. , Bessho Yasumasa , Kageyama Ryoichiro , Ohmori Harunori 
Published: January 2013

Key points
Olfactory receptor neurons (ORNs) utilise the spontaneous firing activity for axonal targeting.
Cyclic AMP‐gated HCN channels depolarised the membranes of ORNs and enhanced their spontaneous firing activity.
Standing activation of the β‐adrenergic receptors maintained the basal cAMP level and resulted in the opening of HCN channels.
The over‐expression of HCN4 resulted in a decrease in the number of glomeruli in the olfactory bulb, which was rescued by suppressing HCN4 over‐expression.
HCN channels, together with the standing activation of G‐protein‐coupled receptors, maintained the spontaneous firing activity of ORNs and were essential to glomerular formation in the olfactory bulb.
Abstract  Olfactory receptor neurons (ORNs), which undergo lifelong neurogenesis, have been studied extensively to understand how neurons form precise topographical networks. Neural projections from ORNs are principally guided by the genetic code, which directs projections from ORNs that express a specific odorant receptor to the corresponding glomerulus in the olfactory bulb. In addition, ORNs utilise spontaneous firing activity to establish and maintain the neural map. However, neither the process of generating this spontaneous activity nor its role as a guidance cue in the olfactory bulb is clearly understood. Utilising extracellular unit‐recordings in mouse olfactory epithelium slices, we demonstrated that the hyperpolarisation‐activated cyclic nucleotide‐gated (HCN) channels in the somas of ORNs depolarise their membranes and boost their spontaneous firing rates by sensing basal cAMP levels; the odorant‐sensitive cyclic nucleotide‐gated (CNG) channels in cilia do not. The basal cAMP levels were maintained via the standing activation of β‐adrenergic receptors. Using a Tet‐off system to over‐express HCN4 channels resulted in the enhancement of spontaneous ORN activity and dramatically reduced both the size and number of glomeruli in the olfactory bulb. This phenotype was rescued by the administration of doxycycline. These findings suggest that cAMP plays different roles in cilia and soma and that basal cAMP levels in the soma are directly converted via HCN channels into a spontaneous firing frequency that acts as an intrinsic guidance cue for the formation of olfactory networks.
A defined heteromeric KV1 channel stabilizes the intrinsic pacemaking and regulates the output of deep cerebellar nuclear neurons to thalamic targets
Authors: Ovsepian Saak V. , Steuber Volker , Le Berre Marie , O’Hara Liam , O’Leary Valerie B. , Dolly J. Oliver 
Published: January 2013

Key points
The result of cerebellar integration is encoded in the output of deep cerebellar nuclear (DCN) neurons in the form of dynamic changes in spontaneous firing rate and pattern.
The soma of these neurons has been demonstrated to be enriched with potassium channels (KV1) produced by mandatory multi‐merization of KV1.1, 1.2 α and KVβ2 subunits.
The outward K+ current (IKV1) mediated by these channels is proven to be a critical stabilizer for both the rate and temporal precision of self‐sustained firing of DCN neurons.
Activated from low‐threshold, IKV1 provides an effective counter‐balance to depolarizing inputs, attenuates the back‐propagating action potentials, favouring dominance of clock‐like somatic pace‐making of these cells – an important condition for accurate encoding of time variant inputs.
The relevance of these observations to physiology and integrative brain mechanisms is shown through a multi‐compartmental neuronal model as well as retro‐axonal tracing of neurons projecting to thalamic relay nuclei.
Abstract  The output of the cerebellum to the motor axis of the central nervous system is orchestrated mainly by synaptic inputs and intrinsic pacemaker activity of deep cerebellar nuclear (DCN) projection neurons. Herein, we demonstrate that the soma of these cells is enriched with KV1 channels produced by mandatory multi‐merization of KV1.1, 1.2 α and KVβ2 subunits. Being constitutively active, the K+ current (IKV1) mediated by these channels stabilizes the rate and regulates the temporal precision of self‐sustained firing of these neurons. Placed strategically, IKV1 provides a powerful counter‐balance to prolonged depolarizing inputs, attenuates the rebound excitation, and dampens the membrane potential bi‐stability. Somatic location with low activation threshold render IKV1 instrumental in voltage‐dependent de‐coupling of the axon initial segment from the cell body of projection neurons, impeding invasion of back‐propagating action potentials into the somato‐dendritic compartment. The latter is also demonstrated to secure the dominance of clock‐like somatic pacemaking in driving the regenerative firing activity of these neurons, to encode time variant inputs with high fidelity. Through the use of multi‐compartmental modelling and retro‐axonal labelling, the physiological significance of the described functions for processing and communication of information from the lateral DCN to thalamic relay nuclei is established.
New Insight into Amphotericin B Resistance in Aspergillus terreus
Authors: Blum Gerhard , Hörtnagl Caroline , Jukic Emina , Erbeznik Thomas , Pümpel Thomas , Dietrich Hermann , Nagl Markus , Speth Cornelia , Rambach Günter , Lass-Flörl Cornelia 
Published: January 2013

ABSTRACT

Amphotericin B (AMB) is the predominant antifungal drug, but the mechanism of resistance is not well understood. We compared the
in vivo
virulence of an AMB-resistant
Aspergillus terreus
(ATR) isolate with that of an AMB-susceptible
A. terreus
isolate (ATS) using a murine model for disseminated aspergillosis. Furthermore, we analyzed the molecular basis of intrinsic AMB resistance
in vitro
by comparing the ergosterol content, cell-associated AMB levels, AMB-induced intracellular efflux, and prooxidant effects between ATR and ATS. Infection of immunosuppressed mice with ATS or ATR showed that the ATS strain was more lethal than the ATR strain. However, AMB treatment improved the outcome in ATS-infected mice while having no positive effect on the animals infected with ATR. The
in vitro
data demonstrated that ergosterol content is not the molecular basis for AMB resistance. ATR absorbed less AMB, discharged more intracellular compounds, and had better protection against oxidative damage than the susceptible strain. Our experiments showed that ergosterol content plays a minor role in intrinsic AMB resistance and is not directly associated with intracellular cell-associated AMB content. AMB might exert its antifungal activity by oxidative injury rather than by an increase in membrane permeation.
The Novel CTX-M-116 β-Lactamase Gene Discovered in Proteus mirabilis Is Composed of Parts of the CTX-M-22 and CTX-M-23 Genes
Authors: Fursova N. , Pryamchuk S. , Kruglov A. , Abaev I. , Pecherskikh E. , Kartsev N. , Svetoch E. , Dyatlov I. 
Published: January 2013

ABSTRACTThe novel β-lactamase geneblaCTX-M-116was identified in aProteus mirabilisnosocomial isolate recovered from the urine of a patient in Moscow in 2005. DNA sequence analysis showedblaCTX-M-116to be a hybrid gene consisting of 5′blaCTX-M-23(nucleotides 1 to 278) and 3′blaCTX-M-22(nucleotides 286 to 876) moieties separated by an intervening putative site of recombination (GTTAAAT). A retrospective analysis of availableblaCTX-Mgenes in the GenBank database revealed 19blaCTX-Mgenes that display the same hybrid structure.
Inhibitory and Fungicidal Effects of Antifungal Drugs against Aspergillus Species in the Presence of Serum
Authors: Elefanti Antigoni , Mouton Johan W. , Krompa Katerina , Al-Saigh Rafal , Verweij Paul E. , Zerva Loukia , Meletiadis Joseph 
Published: January 2013

ABSTRACT

Given the high protein binding rates of antifungal drugs and the effect of serum proteins on
Aspergillus
growth, we investigated the
in vitro
pharmacodynamics of amphotericin B, voriconazole, and three echinocandins in the presence of human serum, assessing both inhibitory and fungicidal effects.
In vitro
inhibitory (IC) and fungicidal (FC) concentrations against 5 isolates of
Aspergillus fumigatus
,
Aspergillus flavus
, and
Aspergillus terreus
were determined with a CLSI M38-A2-based microdilution method using the XTT methodology after 48 h of incubation at 35°C with a medium supplemented with 50% human serum. In the presence of serum, the IC and FC of amphotericin B and the IC of echinocandins were increased (1.21- to 13.44-fold), whereas voriconazole IC and FC were decreased (0.22- to 0.90-fold). The amphotericin B and voriconazole FC/IC ratios did not change significantly (0.59- to 2.33-fold) in the presence of serum, indicating that the FC increase was due to the IC increase. At echinocandin concentrations above the minimum effective concentration (MEC), fungal growth was reduced by 10 to 50% in the presence of human serum, resulting in complete inhibition of growth for some isolates. Thus, the
in vitro
activities of amphotericin B and echinocandins were reduced, whereas that of voriconazole was enhanced, in the presence of serum. These changes could not be predicted by the percentage of protein binding, indicating that other factors and/or secondary mechanisms may account for the observed
in vitro
activities of antifungal drugs against
Aspergillus
species in the presence of serum.
Preclinical Investigations Reveal the Broad-Spectrum Neutralizing Activity of Peptide Pep19-2.5 on Bacterial Pathogenicity Factors
Authors: Heinbockel Lena , Sánchez-Gómez Susana , Martinez de Tejada Guillermo , Dömming Sabine , Brandenburg Julius , Kaconis Yani , Hornef Mathias , Dupont Aline , Marwitz Sebastian , Goldmann Torsten , Ernst Martin , Gutsmann Thomas , Schürholz Tobias , Brandenburg Klaus 
Published: January 2013

ABSTRACT

Bacterial infections are known to cause severe health-threatening conditions, including sepsis. All attempts to get this disease under control failed in the past, and especially in times of increasing antibiotic resistance, this leads to one of the most urgent medical challenges of our times. We designed a peptide to bind with high affinity to endotoxins, one of the most potent pathogenicity factors involved in triggering sepsis. The peptide Pep19-2.5 reveals high endotoxin neutralization efficiency
in vitro
, and here, we demonstrate its antiseptic/anti-inflammatory effects
in vivo
in the mouse models of endotoxemia, bacteremia, and cecal ligation and puncture, as well as in an
ex vivo
model of human tissue. Furthermore, we show that Pep19-2.5 can bind and neutralize not only endotoxins but also other bacterial pathogenicity factors, such as those from the Gram-positive bacterium
Staphylococcus aureus
. This broad neutralization efficiency and the additive action of the peptide with common antibiotics makes it an exceptionally appropriate drug candidate against bacterial sepsis and also offers multiple other medication opportunities.
Regulation of Inhibition of Neutrophil Infiltration by the Two-Component Regulatory System CovRS in Subcutaneous Murine Infection with Group A Streptococcus
Authors: Li Jinquan , Zhu Hui , Feng Wenchao , Liu Mengyao , Song Yingli , Zhang Xiaolan , Zhou Yang , Bei Weicheng , Lei Benfang 
Published: January 2013

ABSTRACT

Hypervirulent invasive group A streptococcus (GAS) isolates inhibit neutrophil infiltration more than pharyngitis isolates do, and the molecular basis of this difference is not well understood. This study was designed to first determine whether natural null mutation of the two-component regulatory system CovRS is responsible for the enhancement of the inhibition of neutrophil recruitment seen in hypervirulent GAS. Next, we examined the role of CovRS-regulated interleukin-8/CXC chemokine peptidase (SpyCEP), C5a peptidase (ScpA), and platelet-activating factor acetylhydrolase (SsE) in the enhanced innate immune evasion. Invasive isolate MGAS5005 induces less neutrophil infiltration and produced a greater lesion area than pharyngitis isolate MGAS2221 in subcutaneous infections of mice. It is known that MGAS5005, but not MGAS2221, has a natural 1-bp deletion in the
covS
gene. Replacement of
covS
Δ1bp
in MGAS5005 with wild-type
covS
resulted in the MGAS2221 phenotype. Deletion of
covS
from MGAS2221 resulted in the MGAS5005 phenotype. Tests of single, double, and triple deletion mutants of the MGAS5005
sse
,
spyCEP
, and
scpA
genes found that SsE plays a more important role than SpyCEP and ScpA in the inhibition of neutrophil recruitment and that SsE, SpyCEP, and ScpA do not have synergistic effects on innate immune evasion by MGAS5005. Deletion of
sse
, but not
spyCEP
or
scpA
, of MGAS2221 enhances neutrophil recruitment. Thus,
covS
null mutations can cause substantial inhibition of neutrophil recruitment by enhancing the expression of the chemoattractant-degrading virulence factors, and SsE, but not SpyCEP or ScpA, is required for CovRS-regulated GAS inhibition of neutrophil infiltration.
Antibodies to gp120 and PD-1 Expression on Virus-Specific CD8
+
T Cells in Protection from Simian AIDS
Authors: Vaccari Monica , Halwani Rabih , Patterson L. Jean , Boasso Adriano , Beal Jennifer , Tryniszewska Elzbieta , Hryniewicz Anna , Venzon David , Haddad Elias K. , El-Far Mohamed , Rosati Margherita , Pavlakis George N. , Felber Barbara K. , Al-Muhsen Saleh , Robert-Guroff Marjorie , Sekaly Rafick-Pierre , Franchini Genoveffa 
Published: January 2013

ABSTRACT

We compared the relative efficacies against simian immunodeficiency virus (SIV) challenge of three vaccine regimens that elicited similar frequencies of SIV-specific CD4
+
and CD8
+
T-cell responses but differed in the level of antibody responses to the gp120 envelope protein. All macaques were primed with DNA plasmids expressing SIV
gag
,
pol
,
env
, and
Retanef
genes and were boosted with recombinant modified vaccinia Ankara virus (MVA) expressing the same genes, either once (1 × MVA) or twice (2 × MVA), or were boosted once with MVA followed by a single boost with replication-competent adenovirus (Ad) type 5 host range mutant (Ad5 h) expressing SIV
gag
and
nef
genes but not
Retanef
or
env
(1 × MVA/Ad5). While two of the vaccine regimens (1 × MVA and 1 × MVA/Ad5) protected from high levels of SIV replication only during the acute phase of infection, the 2 × MVA regimen, with the highest anti-SIV gp120 titers, protected during the acute phase and transiently during the chronic phase of infection. Mamu-A*01 macaques of this third group exhibited persistent Gag CD8
+
CM9
+
effector memory T cells with low expression of surface Programmed death-1 (PD-1) receptor and high levels of expression of genes associated with major histocompatibility complex class I (MHC-I) and MHC-II antigen. The fact that control of SIV replication was associated with both high titers of antibodies to the SIV envelope protein and durable effector SIV-specific CD8
+
T cells suggests the hypothesis that the presence of antibodies at the time of challenge may increase innate immune recruiting activity by enhancing antigen uptake and may result in improvement of the quality and potency of secondary SIV-specific CD8
+
T-cell responses.
Amateur boxing in the last 59 years. Impact of rules changes on the type of verdicts recorded and implications on boxers’ health
Authors: Bianco Massimiliano , Loosemore Mike , Daniele Gianlorenzo , Palmieri Vincenzo , Faina Marcello , Zeppilli Paolo 
Published: January 2013

Background/aimSeveral changes have occurred in Olympic boxing (OB) in the last few decades, influencing the results in official competitions. The aim of this study was to assess how the evolution of rules changed the rate of the results that can influence boxers’ health.MethodsFrom a web-research, the results of OB tournaments from 1952 to 2011 were reviewed (29 357 bouts). For each event, rate of knockout (KO), referee-stop contest (RSC), RSC-Head (RSCH), RSC-Injury (RSCI), RSC-Outclassed (RSCO), abandon, disqualification and points decisions were recorded. In our analysis we investigated the changes that occurred after the introduction of the standing-count rule (1964), mandatory head guard (1984), computerised scoring system (1992), RSCO (2000–2009) and modification of bout formula 3×3 min rounds (3×3, until 1997, 5×2 min rounds (5×2) until 1999, 4×2 min rounds (4×2) until 2008, 3×3 from 2009).ResultsThe most important results were: (1) an RSCI rate increase (0.72–2.42%, p<0.03) after the standing-count rule; (2) a lower RSCI (0.60%, p<0.001) and higher RSCH (1.31–4.92%, p<0.001) and RSC (9.71–13.05%, p<0.03) rate with mandatory head guard; (3) a KO rate reduction (6.44–2.09%, p<0.001) with the computerised scoring system; (4) an RSC (13.15–5.91%, p<0.05) and RSCH (4.23–1.41%, p<0.001) rate reduction comparing 5×2–4×2 bouts.ConclusionsIn the last six decades, along with rule changes in OB, a clear reduction of health challenging results was observed. In the near future, older rules will be adopted (no head guard and a manual scoring system). Continued medical surveillance is important to ensure that new rule changes do not result in poor medical outcomes for the boxers.