Miracle-dz/UniFAR-FTUs huggingface dataset:
A GMCSF‐neuroantigen fusion protein is a potent tolerogen in experimental autoimmune encephalomyelitis (EAE) that is associated with efficient targeting of neuroantigen to APC

Cytokine‐NAg fusion proteins represent an emerging platform for specific targeting of self‐antigen to particular APC subsets as a means to achieve antigen‐specific immunological tolerance. This study focused on cytokine‐NAg fusion proteins that targeted NAg to myeloid APC. Fusion proteins contained GM‐CSF or the soluble extracellular domain of M‐CSF as the N‐terminal domain and the encephalitogenic 69–87 peptide of MBP as the C‐terminal domain. GMCSF‐NAg and MCSF‐NAg fusion proteins were ∼1000‐fold and 32‐fold more potent than NAg in stimulating antigenic proliferation of MBP‐specific T cells, respectively. The potentiated antigenic responses required cytokine‐NAg covalent linkage and receptor‐mediated uptake. That is, the respective cytokines did not potentiate antigenic responses when cytokine and NAg were added as separate molecules, and the potentiated responses were inhibited specifically by the respective free cytokine. Cytokine‐dependent targeting of NAg was specific for particular subsets of APC. GMCSF‐NAg and MCSF‐NAg targeted NAg to DC and macrophages; conversely, IL4‐NAg and IL2‐NAg fusion proteins, respectively, induced an ∼1000‐fold enhancement in NAg reactivity in the presence of B cell and T cell APC. GMCSF‐NAg significantly attenuated severity of EAE when treatment was completed before encephalitogenic challenge or alternatively, when treatment was initiated after onset of EAE. MCSF‐NAg also had significant tolerogenic activity, but GMCSF‐NAg was substantially more efficacious as a tolerogen. Covalent GMCSF‐NAg linkage was required for prevention and treatment of EAE. In conclusion, GMCSF‐NAg was highly effective for targeting NAg to myeloid APC and was a potent, antigen‐specific tolerogen in EAE.
Use of positron emission tomography in localized extremity soft tissue sarcoma treated with neoadjuvant chemotherapy

Patients with high‐grade soft tissue sarcomas are at high risk of developing local disease recurrence and metastatic disease. [F‐18]‐fluorodeoxy‐D‐glucose (FDG) positron emission tomography (PET) scans are hypothesized to detect histopathologic response to therapy and to predict risk of tumor progression in patients with various malignancies. Serial FDG‐PET scans were taken to determine the correlation between FDG uptake and patient outcomes in patients receiving multimodality treatment of extremity sarcomas.
Craniosynostosis Incision: Scalpel or Cautery?

Abstract There is an ongoing debate regarding the optimal instrument for scalp incisions: the scalpel or electrocautery. The argument generally focuses on improved healing after an incision made with a knife and decreased bleeding when using electrocautery. This study compares the use of scalpel and electrocautery in making coronal incisions for patients undergoing surgical correction of craniosynostosis. The outcome metric used is wound healing within 6 months after surgery. All patients presenting to the University of North Carolina Children’s Hospital with craniosynostosis between July 1, 2007 and January 1, 2010 requiring a coronal incision for surgical correction were prospectively enrolled. In all of these patients, half of the coronal incision was made with knife; the other half, with needle tip cautery. Side of the incision was specified at the time of surgery in the operative report. Patients were excluded from the study if the instrument for incision was not specified or if only 1 modality was used for the entire incision. Sixty-eight patients underwent cranial vault reconstruction, of which 58 met inclusion criteria. Of the 58 matched pairs, 55 were analyzed statistically. The 3 excluded cases were those who had midline complications. There were 17 wound complications (15%): 8 in the knife group, 6 in the cautery group, and 3 at midline (with indeterminate side for the problem). We found no statistically significant difference in wound healing between incisions made with a knife or with electrocautery.
Brain temperature exceeds systemic temperature in head-injured patients.

OBJECTIVE To identify the temperature differences in readings taken from the brain, jugular bulb, and core body in head-injured patients. DESIGN Prospective, observational study. SETTING Neurosurgical intensive care unit of a university-affiliated county hospital. PATIENTS Thirty patients with severe head injuries had measurements of brain and core body temperatures. Fourteen patients also had measurements of jugular venous blood at the level of the jugular bulb. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Brain temperature was increased an average of 2.0 degrees F (1.1 degrees C) over the core body temperature. In individual patients, the average brain temperature increase over the core body temperature ranged from -0.5 degrees to 3.8 degrees F (-0.30 degrees to 2.1 degrees C). Jugular vein and core body temperatures were similar. The difference in the brain and body temperatures increased when cerebral perfusion pressure decreased to between 20 and 50 mm Hg. The difference in the brain and body temperatures decreased in those patients treated with barbiturate coma. CONCLUSIONS Direct measurement of temperature in head-injured patients is a safe procedure. Temperatures in the brain are typically increased over the core body temperature and the jugular bulb temperatures. Jugular vein temperature measurement is not a good measurement of brain temperature since it reflects body, not brain temperature. These findings support the potential importance of monitoring brain temperature and the importance of controlling fever in severely head-injured patients since brain temperature may be higher than expected.
Genetic influences on human brain structure: A review of brain imaging studies in twins

Twin studies suggest that variation in human brain volume is genetically influenced. The genes involved in human brain volume variation are still largely unknown, but several candidate genes have been suggested. An overview of structural Magnetic Resonance (brain) Imaging studies in twins is presented, which focuses on the influence of genetic factors on variation in healthy human brain volume. Twin studies have shown that genetic effects varied regionally within the brain, with high heritabilities of frontal lobe volumes (90–95%), moderate estimates in the hippocampus (40–69%), and environmental factors influencing several medial brain areas. High heritability estimates of brain structures were revealed for regional amounts of gray matter (density) in medial frontal cortex, Heschl's gyrus, and postcentral gyrus. In addition, moderate to high heritabilities for densities of Broca's area, anterior cingulate, hippocampus, amygdala, gray matter of the parahippocampal gyrus, and white matter of the superior occipitofrontal fasciculus were reported. The high heritability for (global) brain volumes, including the intracranium, total brain, cerebral gray, and white matter, seems to be present throughout life. Estimates of genetic and environmental influences on age‐related changes in brain structure in children and adults await further longitudinal twin‐studies. For prefrontal cortex volume, white matter, and hippocampus volumes, a number of candidate genes have been identified, whereas for other brain areas, only a few or even a single candidate gene has been found so far. New techniques such as genome‐wide scans may become helpful in the search for genes that are involved in the regulation of human brain volume throughout life. Hum Brain Mapp, 2007. © 2007 Wiley‐Liss, Inc.
A Comparison of Levels of Burden in Indian and White Parents With a Son or Daughter With Schizophrenia

Background: Caregiver burden in mental illness is believed to differ between ethnic groups, but few studies have examined this in schizophrenia in the UK. Aim: To measure burden in British North Indian Sikh and white British parents with a son or daughter with established schizophrenia managed in outpatient care. Method: A cross-cultural cohort study measuring family factors, patient psychopathology and levels of burden and distress. Results: Overall levels of burden were low with no significant differences between the groups. Burden subscale scores showed Indian parents were more affected by psychotic behaviours than white parents. The groups also differed on several sociodemographic variables. Conclusion: In stabilized community patients, the overall extent of burden experienced by both Indian and white parents is low and comparable. However, Indian parents were more burdened by psychotic behaviours. This may be a result of co-residence as Indian patients are more likely to live with their families. Social and economic factors in the country of residence and levels of acculturation may also influence levels of burden and the illness behaviours found most bothersome by parents.
An expanding range of functions for the copper chaperone/antioxidant protein Atox1.

SIGNIFICANCE Antioxidant protein 1 (Atox1 in human cells) is a copper chaperone for the copper export pathway with an essential role in cellular copper distribution. In vitro, Atox1 binds and transfers copper to the copper-transporting ATPases, stimulating their catalytic activity. Inactivation of Atox1 in cells inhibits maturation of secreted cuproenzymes as well as copper export from cells. RECENT ADVANCES Accumulating data suggest that cellular functions of Atox1 are not limited to its copper-trafficking role and may include storage of labile copper, modulation of transcription, and antioxidant defense. The conserved metal binding site of Atox1, CxGC, differs from the metal-binding sites of copper-transporting ATPases and has a physiologically relevant redox potential that equilibrates with the GSH:GSSG pair. CRITICAL ISSUES Tight relationship appears to exist between intracellular copper levels and glutathione (GSH) homeostasis. The biochemical properties of Atox1 place it at the intersection of cellular networks that regulate copper distribution and cellular redox balance. Mechanisms through which Atox1 facilitates copper export and contributes to oxidative defense are not fully understood. FUTURE DIRECTIONS The current picture of cellular redox homeostasis and copper physiology will be enhanced by further mechanistic studies of functional interactions between the GSH:GSSG pair and copper-trafficking machinery.
Single-electron pulses for ultrafast diffraction

Visualization of atomic-scale structural motion by ultrafast electron diffraction and microscopy requires electron packets of shortest duration and highest coherence. We report on the generation and application of single-electron pulses for this purpose. Photoelectric emission from metal surfaces is studied with tunable ultraviolet pulses in the femtosecond regime. The bandwidth, efficiency, coherence, and electron pulse duration are investigated in dependence on excitation wavelength, intensity, and laser bandwidth. At photon energies close to the cathode’s work function, the electron pulse duration shortens significantly and approaches a threshold that is determined by interplay of the optical pulse width and the acceleration field. An optimized choice of laser wavelength and bandwidth results in sub-100-fs electron pulses. We demonstrate single-electron diffraction from polycrystalline diamond films and reveal the favorable influences of matched photon energies on the coherence volume of single-electron wave packets. We discuss the consequences of our findings for the physics of the photoelectric effect and for applications of single-electron pulses in ultrafast 4D imaging of structural dynamics.
Phosphatidylinositol 3-kinase inhibition enhances human sperm motility.

BACKGROUND The number of spermatozoa with forward motility after capacitation procedures represents the limiting factor for application of IVF versus intracytoplasmatic sperm injection (ICSI) procedure in cases of oligoasthenozoospermia. The possibility of increasing this number may thus be of help to the patient. A complex array of signalling pathways is involved in the regulation of sperm motility and recent data pointed out an important role for kinase/phosphatase-regulated phosphorylation of proteins. Here, we investigated the role of phosphatidylinositol 3-kinase (PI3K), a lipid and protein kinase involved in the regulation of several biological aspects of somatic cells, on human sperm motility by using the specific PI3K inhibitor LY294002. METHODS AND RESULTS We demonstrated that in-vitro incubation of swim-up selected or unselected human spermatozoa with LY294002 determined an increase of percentage forward motility in all the treated samples. The effect was dose-dependent with an EC(50) of 1.09 +/- 0.54 micromol/l. LY294002 also increased sperm movement characteristics and hyperactivation as evaluated by computer-assisted motion analyser. The compound was also able to overcome the detrimental effect of hydrogen peroxide and lithium chloride on sperm motility. CONCLUSIONS Our results suggest a negative role for PI3K in the development and maintenance of sperm motility and suggest a possible use of PI3K inhibitors to enhance motility in cases of asthenozoospermia.
Retrograde amnesia and the volume of critical brain structures

There are many controversies concerning the structural basis of retrograde amnesia (RA). One view is that memories are held briefly within a medial temporal store (“hippocampal complex”) before being “consolidated” or reorganised within temporal neocortex and/or networks more widely distributed within the cerebral cortex. An alternative view is that the medial temporal lobes are always involved in the storage and retrieval (reactivation) of autobiographical memories (multiple trace theory). The present study used quantitative magnetic resonance imaging (MRI) in 40 patients with focal pathology/volume loss in different sites, to examine the correlates of impairment on three different measures of RA. The findings supported the view that widespread neural networks are involved in the storage and retrieval of autobiographical and other remote memories. Brain volume measures in critical structures could account for 60% of variance on autobiographical memory measures (for incidents and facts) in diencephalic patients and for 60–68% of variance in patients with frontal lesions. Significant correlations with medial temporal lobe volume were found only in the diencephalic group, in whom they were thought to reflect thalamic changes, but not in patients with herpes encephalitis or hypoxia in whom the temporal lobes were particularly implicated. The latter finding fails to support one of the main predictions of multiple trace theory, as presently expounded. © 2003 Wiley‐Liss, Inc.
The impacts of Japanese food losses and food waste on global natural resources and greenhouse gas emissions

Japan depends heavily on imports for its food supply. Since 2000, the food self‐sufficiency ratio has remained approximately 40% on a caloric basis. Japanese food wastage (i.e., food losses and food waste) is estimated to have been 6.42 million tonnes (50 kg per capita of wastage) in 2012. These values indicate that food wastage leads to wasted natural resources and excessive greenhouse gas (GHG) emissions both in Japan and in countries that export to Japan. This study estimates Japanese food wastage by food item to evaluate impacts on land and water resources and global GHG emissions during the processing, distribution, and consumption phases of the food supply chain while also considering the feed crops needed for livestock production. Despite uncertainties due to data limitations, in 2012, 1.23 million hectares of harvested land were used to produce food that was eventually wasted, and 413 million m3 of water resources were wasted due to Japanese food wastage in agricultural production. Furthermore, unnecessary GHG emissions were 3.51 million tonnes of CO2 eq. in agricultural production and 0.49 million tonnes of CO2 eq. in international transportation. The outcomes of the present study can be used to develop countermeasures to food wastage in industrializing Asian countries where food imports are projected to increase and food wastage issues in the consumption stage are expected to become as serious as they currently are in Japan.
Endothelial-Directed Hepatic Regeneration After Partial Hepatectomy

ObjectiveTo determine the role of the microvascular endothelium in the regulation of regenerating liver mass after partial hepatectomy. Summary Background DataAngiogenesis is critical for both pathologic and physiologic processes. The ability of certain tissues, such as the liver, kidney, and spleen, to regenerate after injury is poorly understood. The liver will regenerate to its normal mass within 8 days of surgical excision. Because the authors have previously shown that the endothelial cell regulates tumor mass, we hypothesized that normal adult organ mass is also controlled by the endothelial cell. MethodsTwo-thirds partial hepatectomy was performed in 7- to 8-week-old C57 BL/6 mice, followed by systemic treatment with either the angiogenesis stimulator basic fibroblast growth factor (bFGF) (1 &mgr;g/g/d intraperitoneal) or the angiogenesis inhibitor TNP-470 (30 mg/kg/qod subcutaneous). Groups of three mice were then euthanized on postoperative days 2, 4, 6, and 8, and the livers were weighed and analyzed by immunohistochemistry. ResultsbFGF accelerated hepatic regeneration by 42%, 19%, 16%, and 16% on postoperative days 2, 4, 6, and 8, respectively. TNP-470 inhibited hepatic regeneration by 46%, 74%, 67%, and 64% on postoperative days 2, 4, 6, and 8, respectively. Immunohistochemistry revealed that bFGF and TNP-470 primarily affected the endothelial compartment. Specifically, bFGF increased endothelial proliferation and decreased endothelial apoptosis. TNP-470, in contrast, inhibited endothelial cell proliferation. The cessation of the regenerative process correlated with a decrease in endothelial proliferation and an increase in endothelial apoptosis. ConclusionsThe systemic administration of angiogenesis agents modulates the regeneration of hepatic mass primarily by affecting endothelial cell proliferation or apoptosis. Endothelial cell apoptosis is associated with the cessation of the regenerative process in control mice. These results suggest that the endothelial cell is one of the key mediators of regenerating adult tissue mass in this partial hepatectomy model.
Mind the Gap: Stated versus Revealed Donations and the Differential Role of Behavioral Factors

This paper uses a contingent valuation study and an actual donation request to assess the impact of behavioral factors on hypothetical bias in stated willingness-to-pay estimates. Our findings indicate that both the number of respondents willing to donate and the amount they are willing to donate differ substantially between treatments. Behavioral factors play a substantial and significant role; in particular, the extent of warm glow derived from giving and expectations about other people’s behavior increase the extent of hypothetical bias in stated willingness-to-pay estimates. We suggest ways in which this may be incorporated in future contingent valuation study design. (JEL Q51)
Behavioural phenotyping of knockout mice for the sigma-1 (σ1) chaperone protein revealed gender-related anxiety, depressive-like and memory alterations

The sigma-1 (σ1) protein regulates calcium homeostasis and acts as an endoplasmic reticulum chaperone. It can be activated by ligands which impact memory, depression, anxiety or addiction processes. We here characterized the behavioural phenotype of knockout (KO) mice for the σ1 protein. Two-month old male σ1 −/− mice showed signs of anxiety in the open-field, passive avoidance or elevated plus-maze test, but other activity or memory responses were unchanged. Female σ1 −/− mice showed deficits in spontaneous alternation or water-maze learning. Twelve-month old σ1 +/− female mice showed deficits in alternation and σ1 −/− mice in avoidance escape latency. Two- and 14-month old female σ1 −/− mice showed decreased plasma 17β-estradiol levels. Treatment with 17β-estradiol (0.1, 0.2 mg/kg i.p.) reversed the spatial memory deficits in young and aged mice. Male σ1 KO mice showed enhanced response in the forced swimming test. Igmesine, a σ1 agonist, failed to decrease immobility in σ1 KO mice. Fluoxetine and sertraline were more efficient in σ1 KO mice, an effect likely related to their σ1 antagonist activity. Imipramine, desipramine and amitriptyline were equally active. σ1 Protein invalidation therefore affected stress or anxiety response but not memory in males. Changes in steroid tonus in female animals led, however, to memory impairments that increased with age.
Vestibular evoked myogenic potential according to middle ear condition in chronic otitis media with tympanic membrane perforation

Abstract Conclusion: Vestibular evoked myogenic potential (VEMP) function results can vary between individuals with different middle ear conditions. Therefore, by analyzing VEMP results after paper patching, we can predict the condition of the middle ear in chronic otitis media (COM) patients. Objectives: VEMP responses decrease with impairment of sound transmission, such as in conductive hearing loss (CHL). COM with tympanic membrane (TM) perforation is a common disorder that causes various degrees of CHL. The aim of this study was to evaluate and clarify the VEMP responses in patients with COM with different middle ear pathology. Methods: This study included 50 patients with unilateral COM with TM perforation. Initial pure-tone audiometry (PTA) and VEMP responses were recorded. After paper patching, PTA and VEMP were re-performed. Each VEMP response was compared with those of the healthy controls. Moreover, VEMP responses between pre- and post-paper patching were compared. Results: There was a positive correlation between normalizing of VEMP parameters, such as p13 and VEMP asymmetry ratio (VAR), and reduction of air–bone gap in patients with COM after paper patching. The VEMP response in patients with COM with intact ossicle and clean mucosa was more normalized compared with those in patients with COM with different middle ear conditions.
Train stimulation of parallel fibre to Purkinje cell inputs reveals two populations of synaptic responses with different receptor signatures

Purkinje cells of the cerebellum receive ∼180,000 parallel fibre synapses, which have often been viewed as a homogeneous synaptic population and studied using single action potentials. Many parallel fibre synapses might be silent, however, and granule cells in vivo fire in bursts. Here, we used trains of stimuli to study parallel fibre inputs to Purkinje cells in rat cerebellar slices. Analysis of train EPSCs revealed two synaptic components, phase 1 and 2. Phase 1 is initially large and saturates rapidly, whereas phase 2 is initially small and facilitates throughout the train. The two components have a heterogeneous distribution at dendritic sites and different pharmacological profiles. The differential sensitivity of phase 1 and phase 2 to inhibition by pentobarbital and NBQX mirrors the differential sensitivity of AMPA receptors associated with the transmembrane AMPA receptor regulatory protein, γ‐2, gating in the low‐ and high‐open probability modes, respectively.