bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human phase response curve to a single 6.5 h pulse of short‐wavelength light
Authors: Rüger Melanie , St Hilaire Melissa A. , Brainard George C. , Khalsa Sat‐Bir S. , Kronauer Richard E. , Czeisler Charles A. , Lockley Steven W. 
Published: October 2012

Key points
The human ∼24 h circadian pacemaker ensures appropriate timing of physiological, behavioural and metabolic events and is synchronized to the 24 h day primarily by the 24 h light–dark cycle.
The direction and magnitude of photic resetting depend on the timing of light exposure, and are described by a phase response curve (PRC).
The human circadian photoreception system is functionally and anatomically distinct from the visual system and employs a novel photoreceptor, melanopsin, which is maximally sensitive to short‐wavelength (blue) visible light.
We constructed a PRC to 6.5 h of blue (480 nm) light and compared it with a prior 6.7 h white light PRC; the blue light PRC achieved ∼75% of the resetting response of the white light PRC.
This study suggests that short‐wavelength visible light exposures may be more efficient than traditional high‐intensity white light exposures for treatment of circadian rhythm sleep disorders.
Abstract  The photic resetting response of the human circadian pacemaker depends on the timing of exposure, and the direction and magnitude of the resulting shift is described by a phase response curve (PRC). Previous PRCs in humans have utilized high‐intensity polychromatic white light. Given that the circadian photoreception system is maximally sensitive to short‐wavelength visible light, the aim of the current study was to construct a PRC to blue (480 nm) light and compare it to a 10,000 lux white light PRC constructed previously using a similar protocol. Eighteen young healthy participants (18–30 years) were studied for 9–10 days in a time‐free environment. The protocol included three baseline days followed by a constant routine (CR) to assess initial circadian phase. Following this CR, participants were exposed to a 6.5 h 480 nm light exposure (11.8 μW cm−2, 11.2 lux) following mydriasis via a modified Ganzfeld dome. A second CR was conducted following the light exposure to re‐assess circadian phase. Phase shifts were calculated from the difference in dim light melatonin onset (DLMO) between CRs. Exposure to 6.5 h of 480 nm light resets the circadian pacemaker according to a conventional type 1 PRC with fitted maximum delays and advances of −2.6 h and 1.3 h, respectively. The 480 nm PRC induced ∼75% of the response of the 10,000 lux white light PRC. These results may contribute to a re‐evaluation of dosing guidelines for clinical light therapy and the use of light as a fatigue countermeasure.
Regulation of synaptic transmission at the photoreceptor terminal: a novel role for the cation–chloride co‐transporter NKCC1
Authors: Shen Wen , Purpura Lauren A. , Li Baoqin , Nan Changlong , Chang Irene J. , Ripps Harris 
Published: October 2012

Key points
The Cl− uptake cotransporter, Na+–K+–2Cl− type 1 (NKCC1), is expressed in the distal synaptic layer of the vertebrate retina, where photoreceptor terminals contact the dendrites of horizontal and bipolar cells.
Light adaptation, dopamine and a D1 receptor agonist increased the expression levels of phosphorylated NKCC1, the active form of the transporter inserted in the cell membrane.
Pharmacological blockage of NKCC1 with bumetanide increased the rod‐ and cone‐mediated excitatory postsynaptic currents in horizontal cells.
Inhibiting NKCC1 increased exocytotic membrane capacitance, intracellular Ca2+ levels, and voltage‐dependent Ca2+ channel currents in both rod and cone terminals, all of which are associated with increased transmitter release.
This study describes a new function of NKCC1, specifically the suppression of transmitter release at the photoreceptor terminals, a process that serves to prevent the depletion of glutamate and protect retinal neurons from its putative cytotoxic effects.
Abstract  The Na+–K+–2Cl− co‐transporter type 1 (NKCC1) is localized primarily throughout the outer plexiform layer (OPL) of the distal retina, a synaptic lamina that is comprised of the axon terminals of photoreceptors and the dendrites of horizontal and bipolar cells. Although known to play a key role in development, signal transmission and the gating of sensory signals in other regions of the retina and in the CNS, the contribution of NKCC1 to synaptic transmission within the OPL is largely unknown. In the present study, we investigated the function of NKCC1 at the photoreceptor–horizontal cell synapse by recording the electrical responses of photoreceptors and horizontal cells before and after blocking the activity of the transporter with bumetanide (BMN). Because NKCC1 co‐transports 1 Na+, 1 K+ and 2 Cl−, it is electroneutral and its activation had little effect on membrane conductance. However, recordings from postsynaptic horizontal cells revealed that inhibiting NKCC1 with BMN greatly increased glutamate release from both rod and cone terminals. In addition, we found that NKCC1 directly regulates Ca2+‐dependent exocytosis at the photoreceptor synapse, raising the possibility that NKCC1 serves to suppress bulk release of glutamate vesicles from photoreceptor terminals in the dark and at light offset. Interestingly, NKCC1 gene and protein expressions were upregulated by light, which we attribute to the light‐induced release of dopamine acting on D1‐like receptors. In sum, our study reveals a new role for NKCC1 in the regulation of synaptic transmission in photoreceptors.
Do calcium waves propagate between cells and synchronize alternating calcium release in rat ventricular myocytes?
Authors: Li Y. , Eisner D. A. , O’Neill S. C. 
Published: October 2012

Key points
In cell pairs isolated from rat ventricular muscle, spontaneous waves of Ca2+‐induced Ca2+ release are much more likely to propagate between cells connected side to side than end to end.
Investigation of this difference using fluorescence techniques shows that the end‐to‐end connection probably contains the intercalated disc. It is this structure that accounts for the greater distance between sarcoplasmic reticulum Ca2+ release units being so large (about 2.3 μm). At side‐to‐side connections, this distance is much less (about 1.6 μm). This variation may be the cause of the difference in propagation properties.
In cell pairs isolated from rat ventricular muscle, we have been able to induce systolic Ca2+ alternans in‐phase between the cells in a pair. This is not due to propagation of Ca2+ waves between cells. In some cases, wave propagation can interfere with synchrony.
Abstract  The aim was to investigate the propagation of Ca2+ waves between cells and determine whether this synchronizes alternating Ca2+ release between cells. Experiments were carried out on electrically coupled cell pairs; spontaneous Ca2+ waves were produced by elevating external Ca2+. There was a significant difference in the ability of these waves to propagate between cells depending on the orientation of the pairs. Although almost all pairs connected by side‐to‐side contacts showed propagating Ca2+ release, this was very uncommon in end‐to‐end cell pairs. Confocal studies showed that there was a gap at the intercalated disc consisting of cell membranes and a region of cytoplasm devoid of sarcoplasmic reticulum. This gap was 2.3 μm in length and is suggested to interfere with Ca2+ wave propagation. The gap measured was much smaller between side‐to‐side contacts: 1.5 μm and so much less likely to interfere with propagation. Subsequent experiments investigated the synchronization between cells of Ca2+ alternans produced by small depolarizing pulses. Although this alternation results from beat‐to‐beat alternation of intracellular Ca2+ wave propagation, there was no evidence that propagation of Ca2+ waves between cells contributed to synchronization of this alternans.
Double dislocation of finger interphalangeal joints
Authors: Jahangiri Saqib Aziz , Mestha Prabhakar , McNally Scarlett 
Published: October 2012

A 62-year-old, right-hand-dominant man who had dementia and lived in an Elderly Mentally Infirm (EMI) nursing home was admitted through Accident & Emergency (A&E) department following unwitnessed injury to the left little finger.His examination revealed a swollen and deformed left little finger with a laceration along the middle crease on the volar aspect and head of proximal phalanx visible through this. Distally sensations and capillary refill was normal. X-rays showed a double dislocation of both proximal and distal interphalangeal joints. The finger was reduced under ring block and the laceration was washed with saline in A&E. The patient was taken to the operation theatre next morning for wound exploration and wash-out±stabilistion of the finger under general anaesthesia.The wound was thoroughly washed out and closed with 4/0 interrupted nylon. The finger was immobilised with neighbour strapping and bandaged in flexion.
Improved methods for axenic culture of Labyrinthula terrestris, causal agent of rapid blight of turfgrasses
Authors: Yadagiri Kirthi Kiran , Kerrigan Julia , Martin S. Bruce 
Published: October 2012

The genus Labyrinthula is a group of unicellular microorganisms with spindle-shaped cells that move in an ectoplasmic network. Most Labyrinthula species are saprotrophic and found in coastal marine or estuarine habitats; however, exceptions exist, such as Labyrinthula terrestris , a terrestrial plant pathogen that causes rapid blight on cool-season turfgrasses. Labyrinthula spp. can be grown in culture, which facilitates studies on their biology and pathology. However, axenic culture of L. terrestris has always been challenging. We modified the most commonly used Labyrinthula growth medium, serum seawater agar (SSA), and designed 2 media for improved pure culture, modified SSA (MSSA) and grass extract SSA (GESSA). A comparative assessment of these 2 media and basic SSA was made to measure the growth responses of 18 L. terrestris isolates. Results indicate that the average colony area was greatest on GESSA followed by MSSA, while cultures lived longest on MSSA followed by GESSA. We also suggest an improved long-term culture technique to maintain viable L. terrestris isolates for at least 2 years.
Purines, Purinergic Receptors, and Cancer
Authors: Di Virgilio Francesco 
Published: October 2012

Abstract
Purines were long thought to be restricted to the intracellular compartment, where they are used for energy transactions, nucleic acid synthesis, and a multiplicity of biochemical reactions. However, it is now clear that both adenosine and adenosine triphosphate are (i) abundant biochemical components of the tumor microenvironment, (ii) potent modulators of immune cell responses and cytokine release, and (iii) key players in host–tumor interaction. Moreover, both ATP and adenosine directly affect tumor cell growth. Adenosine is a powerful immunosuppressant (mainly acting at A2A receptors) and a modulator of cell growth (mainly acting at A3 receptors). ATP is a proinflammatory (acting at P2Y1, P2Y2, P2Y4, P2Y6, and P2Y12, and at P2X4 and P2X7 receptors), an immunosuppressant (acting at P2Y11), and a growth-promoting agent (acting at P2Y1, P2Y2, and P2X7 receptors). This complex signaling network generates an array of inhibitory and stimulatory responses that affect immune cell function, tumor growth, and metastatic dissemination. Investigation of purinergic signaling has increased our understanding of the tumor microenvironment and opened new and exciting avenues for the development of novel therapeutics. Cancer Res; 72(21); 5441–7. ©2012 AACR.
Preventing Postoperative Metastatic Disease by Inhibiting Surgery-Induced Dysfunction in Natural Killer Cells
Authors: Tai Lee-Hwa , de Souza Christiano Tanese , Bélanger Simon , Ly Lundi , Alkayyal Almohanad A. , Zhang Jiqing , Rintoul Julia L. , Ananth Abhirami A. , Lam Tiffany , Breitbach Caroline J. , Falls Theresa J. , Kirn David H. , Bell John C. , Makrigiannis Andrew P. , Auer Rebecca A. 
Published: October 2012

Abstract
Natural killer (NK) cell clearance of tumor cell emboli following surgery is thought to be vital in preventing postoperative metastases. Using a mouse model of surgical stress, we transferred surgically stressed NK cells into NK-deficient mice and observed enhanced lung metastases in tumor-bearing mice as compared with mice that received untreated NK cells. These results establish that NK cells play a crucial role in mediating tumor clearance following surgery. Surgery markedly reduced NK cell total numbers in the spleen and affected NK cell migration. Ex vivo and in vivo tumor cell killing by NK cells were significantly reduced in surgically stressed mice. Furthermore, secreted tissue signals and myeloid-derived suppressor cell populations were altered in surgically stressed mice. Significantly, perioperative administration of oncolytic parapoxvirus ovis (ORFV) and vaccinia virus can reverse NK cell suppression, which correlates with a reduction in the postoperative formation of metastases. In human studies, postoperative cancer surgery patients had reduced NK cell cytotoxicity, and we show for the first time that oncolytic vaccinia virus markedly increases NK cell activity in patients with cancer. These data provide direct in vivo evidence that surgical stress impairs global NK cell function. Perioperative therapies aimed at enhancing NK cell function will reduce metastatic recurrence and improve survival in surgical cancer patients. Cancer Res; 73(1); 97–107. ©2012 AACR.
Single-Molecule Genomic Data Delineate Patient-Specific Tumor Profiles and Cancer Stem Cell Organization
Authors: Sottoriva Andrea , Spiteri Inmaculada , Shibata Darryl , Curtis Christina , Tavaré Simon 
Published: October 2012

Abstract
Substantial evidence supports the concept that cancers are organized in a cellular hierarchy with cancer stem cells (CSC) at the apex. To date, the primary evidence for CSCs derives from transplantation assays, which have known limitations. In particular, they are unable to report on the fate of cells within the original human tumor. Because of the difficulty in measuring tumor characteristics in patients, cellular organization and other aspects of cancer dynamics have not been quantified directly, although they likely play a fundamental role in tumor progression and therapy response. As such, new approaches to study CSCs in patient-derived tumor specimens are needed. In this study, we exploited ultradeep single-molecule genomic data derived from multiple microdissected colorectal cancer glands per tumor, along with a novel quantitative approach to measure tumor characteristics, define patient-specific tumor profiles, and infer tumor ancestral trees. We show that each cancer is unique in terms of its cellular organization, molecular heterogeneity, time from malignant transformation, and rate of mutation and apoptosis. Importantly, we estimate CSC fractions between 0.5% and 4%, indicative of a hierarchical organization responsible for long-lived CSC lineages, with variable rates of symmetric cell division. We also observed extensive molecular heterogeneity, both between and within individual cancer glands, suggesting a complex hierarchy of mitotic clones. Our framework enables the measurement of clinically relevant patient-specific characteristics in vivo, providing insight into the cellular organization and dynamics of tumor growth, with implications for personalized patient care. Cancer Res; 73(1); 41–49. ©2012 AACR.
Assessment of the F9 genotype-specific FIX inhibitor risks and characterisation of 10 novel severe F9 defects in the first molecular series of Argentinian patients with haemophilia B
Authors: Rossetti Liliana Carmen , Abelleyro Miguel Martín , Candela Miguel , Bianco Raúl Pérez , Pinto Miguel de Tezanos , Larripa Irene Beatriz , Goodeve Anne , Brasi Carlos Daniel De , Radic Claudia Pamela 
Published: October 2012

SummaryIn haemophilia B (HB) (factor IX [FIX] deficiency), F9 genotype largely determines clinical phenotype. Aimed to characterise Argentinian families with HB, this study presents F9 genotype frequencies and their specific FIX inhibitor risk and 10 novel F9 mutations. Ninety-one DNA samples from HB patients and relatives were subjected to a new scheme: a primary screen for large deletions, a secondary screen for point mutations using conformation sensitive gel electrophoresis, DNA-sequencing and bioinformatic analysis. Our unbiased HB population (N=52) (77% with severe, 11.5% moderate and 11.5% mild HB) showed 32 missense (61.5%), including three novel mutations predicting specific structural/functional defects in silico, seven nonsense (13.5%) (one novel), five large deletions, four splice including three novel mutations affecting predicted splicing scores, three indels (two novel) and one Leiden mutation. Our comprehensive HB population included five patients with long-lasting FIX inhibitors: three nonsense (p.E35* (novel), p.R75*, p.W240*) and two entire-F9 deletions. Another patient with an indel (p.A26Rfs*14) developed transient inhibitors. A case-control analysis, based on our global prevalence of 3.05% for developing inhibitors in HB revealed that missense mutations were associated with a low risk odds ratio (OR) of 0.05 and a prevalence of 0.39%, whereas nonsense and entire-F9 deletions had significantly higher risks (OR 11.0 and 32.7) and prevalence (14.3% and 44.5%, respectively). Our cost-effective practical approach enabled identification of the causative mutation in all 55 Argentine families with HB, analysis of the molecular pathology of novel F9 defects and determination of mutation-associated FIX inhibitor risks.
Phenotypic characterisation of pro-inflammatory monocytes and dendritic cells in peripheral arterial disease
Authors: Obst Viviane , Doppler Christopher , Radmacher Marie-Christine , Scheer Martin , Radsak Markus , Gori Tommaso , Warnholtz Ascan , Fottner Christian , Daiber Andreas , Münzel Thomas , Espinola-Klein Christine , Dopheide Jörn 
Published: October 2012

SummaryAtherosclerosis is a chronic inflammatory process involving antigen-presenting cells like monocytes and dendritic cells (DC). The aim of this study was to perform a phenotypic characterisation of these cell types in patients with different degrees of peripheral arterial disease (PAD). Sixty patients with PAD [N= 30 intermittent claudication (IC), N= 30 critical limb ischemia (CLI)] and 30 controls were included. Peripheral blood leucocytes were analysed from peripheral blood by flow cytometry using different gating strategies to directly identify and analyse monocytes, myeloid DC, (mDC) and plasmacytoid DC (pDC). PAD patients showed a significantly higher proportion of proinflammatory CD14++CD16+ monocytes (p<0.0001) compared with healthy individuals. We found an increased number of mDC/ml and a reduced number of pDC/ml (both p<0.01) in PAD patients, leading to a shift in the mDC/pDC ratio (p<0.01). As compared to patients with intermittent claudication, CLI patients presented a reduced expression of HLA-DR (p<0.01), CD86 and CD40 on both mDCs and pDCs (p<0.01). Peripheral blood monocytes show a proinflammatory phenotype in PAD patients compared to controls. In contrast, CLI patients show a reduced expression of proinflammatory markers. We hypothesise that severe ischaemia and/or prolonged inflammation in CLI might lead to a paradoxical attenuation in the proinflammatory membrane pattern of circulating mononuclear cells, possibly hindering an adequate regulatory function of mDCs and pDCs and favouring the progression of disease.
Neural Activity in Superior Parietal Cortex during Rule-based Visual-motor Transformations
Authors: Hawkins Kara M. , Sayegh Patricia , Yan Xiaogang , Crawford J. Douglas , Sergio Lauren E. 
Published: October 2012

Abstract
Cognition allows for the use of different rule-based sensorimotor strategies, but the neural underpinnings of such strategies are poorly understood. The purpose of this study was to compare neural activity in the superior parietal lobule during a standard (direct interaction) reaching task, with two nonstandard (gaze and reach spatially incongruent) reaching tasks requiring the integration of rule-based information. Specifically, these nonstandard tasks involved dissociating the planes of reach and vision or rotating visual feedback by 180°. Single unit activity, gaze, and reach trajectories were recorded from two female Macaca mulattas. In all three conditions, we observed a temporal discharge pattern at the population level reflecting early reach planning and on-line reach monitoring. In the plane-dissociated task, we found a significant overall attenuation in the discharge rate of cells from deep recording sites, relative to standard reaching. We also found that cells modulated by reach direction tended to be significantly tuned either during the standard or the plane-dissociated task but rarely during both. In the standard versus feedback reversal comparison, we observed some cells that shifted their preferred direction by 180° between conditions, reflecting maintenance of directional tuning with respect to the reach goal. Our findings suggest that the superior parietal lobule plays an important role in processing information about the nonstandard nature of a task, which, through reciprocal connections with precentral motor areas, contributes to the accurate transformation of incongruent sensory inputs into an appropriate motor output. Such processing is crucial for the integration of rule-based information into a motor act.
Description of Comprehensive PPTCT Counsellors’ Training: The Backbone of PPTCT Services in India
Authors: Solomon Eileen , Visnegarwala Fehmida , Philip Philimol , Pappachen Jisha Susan , Alexander Glory 
Published: October 2012

Counselling prior to and after HIV testing is an important component of Prevention of Parent to Child Transmission (PPTCT) services. ASHA Foundation, a non-governmental organization (NGO), has been providing PPTCT services since 2002. This includes training of counsellors. The training workshop of 12-days duration comprises of an overview of HIV/AIDS counselling skills, pre- and post-test counselling in the context of PPTCT, supportive counselling for HIV-positive women and their families, universal precautions and recording and documentation. We present the data on paired pre- and post-workshop score results on knowledge of PPTCT among 85 trained counsellors using the National AIDS Control Organization (NACO) questionnaire. The mean pre-test score was 16.6 and post-test was 26.9 from a maximum of 39, with a mean percentage change of 26.5 per cent, for the questions focused on PPTCT, which was significantly different from the mean percentage change of 13.5 per cent in the non-PPTCT questions ( p < 0.05). This showed that training improved their knowledge in PPTCT considerably. Studies to evaluate attitudes, skills and cost effectiveness of a holistic model of PPTCT training need to be undertaken, especially in the wake of the new PPTCT, World Health Organization (WHO) guidelines.