Miracle-dz/UniFAR-FTUs huggingface dataset:
PTP1B Targets the Endosomal Sorting Machinery

Dephosphorylation and endocytic down-regulation are distinct processes that together control the signaling output of a variety of receptor tyrosine kinases (RTKs). PTP1B can directly dephosphorylate several RTKs, but it can also promote activation of downstream pathways through largely unknown mechanisms. These positive signaling functions likely contribute to the tumor-promoting effect of PTP1B in mouse cancer models. Here, we have identified STAM2, an endosomal protein involved in sorting activated RTKs for lysosomal degradation, as a substrate of PTP1B. PTP1B interacts with STAM2 at defined phosphotyrosine sites, and knockdown of PTP1B expression augments STAM2 phosphorylation. Intriguingly, manipulating the expression and phosphorylation state of STAM2 did not have a general effect on epidermal growth factor (EGF)-induced EGF receptor trafficking, degradation, or signaling. Instead, phosphorylated STAM2 specifically suppressed Akt activation, and a phosphorylation-deficient STAM2 mutant displayed prolonged localization on endosomes following EGF stimulation. These results reveal a novel link between the dephosphorylation and endocytic machinery and suggest that PTP1B can affect RTK signaling in a previously unrecognized manner.
Detection of substance P in human tears by laser desorption mass spectrometry and immunoassay.

PURPOSE To determine whether substance P is present in human tears. METHODS Tear samples (1-2 microliters) were collected from one eye of each of 12 subjects. Two of the eyes had dry eye syndrome, two wore contact lenses and had dry eye syndrome, and eight were normal. Five of the eight normal eyes were scheduled to undergo excimer laser refractive surgery, and tears were collected from these eyes before and after surgery. Tear samples were analyzed by laser desorption mass spectrometry. Pooled samples from one individual were subjected to enzyme-linked immunoabsorbent assay. RESULTS Laser desorption mass spectra of the 18 tear samples displayed well defined peaks with mass to charge (m/z) ratios ranging from 1343.7 to 1355.9 and/or 1356.9 to 1364.7, corresponding to an average m/z of 1349.8 +/- 1.13 for protonated substance P and 1361.2 +/- 0.54 for oxidized substance P obtained from 14 mass spectra of standards formulated with substance P concentrations ranging from 10(-4) M to 10(-12) M. As confirmation, an enzyme-linked immunoabsorbent assay performed twice on pooled tears from one eye detected substance P in both replicates at a concentration of 125 pg/ml (9.26 x 10(-11) M). CONCLUSIONS These findings demonstrate that substance P is a component of tears obtained from normal eyes of men and women ranging in age from 26 to 60 years, from eyes fitted with contact lenses, from eyes with dry eye syndrome, and from eyes 1 and 2 days after excimer laser refractive surgery. Whether the concentration of substance P in tears varies with sex, age, or eye condition, the source of substance P in tears, and its role in tears remains to be discovered.
Improvement and quantitative performance estimation of the back support muscle suit

We have been developing the wearable muscle suit for direct and physical motion supports. The use of the McKibben artificial muscle has opened the way to the introduction of “muscle suits” compact, lightweight, reliable, wearable “assist-bots” enabling manual worker to lift and carry weights. Since back pain is the most serious problem for manual worker, improvement of the back support muscle suit under the feasibility study and quantitative estimation are shown in this paper. The structure of the upper body frame, the method to attach to the body, and the axes addition were explained as for the improvement. In the experiments, we investigated quantitative performance results and efficiency of the back support muscle suit in terms of vertical lifting of heavy weights by employing integral electromyography (IEMG). The results indicated that the values of IEMG were reduced by about 40% by using the muscle suit.
A wheelchair with lever propulsion control for climbing up and down stairs

This study proposes a novel stair-climbing wheelchair based on lever propulsion control using the human upper body. Wheelchairs are widely used as supporting locomotion devices for people with acquired lower limb disabilities. However, steps and stairs are critical obstacles to locomotion, which restrict their activities when using wheelchairs. Previous research focused on power-assisted, stair-climbing wheelchairs, which were large and heavy due to its large actuators and mechanisms. In the previous research, we proposed a wheelchair with lever propulsion mechanism and presented its feasibility of climbing up the stairs. The developed stair-climbing wheelchair consists of manual wheels with casters for planar locomotion and a rotary-leg mechanism based on lever propulsion that is capable of climbing up stairs. The wheelchair also has a passive mechanism powered by gas springs for posture transition to shift the user's center of gravity between the desired positions for planar locomotion and stair-climbing. In this paper, we present an advanced study on both climbing up and going down using lever propulsion control by the user's upper body motion. For climbing down the stairs, we reassembled one-way clutches used for the rotary-leg mechanism to help a user climb down the stairs through lever operation. We also equipped the wheelchair with sufficient torque dampers. The frontal wheels were fixed while climbing down the stairs to ensure safety. Relevant experiments were then performed to investigate its performance and verify that the wheelchair users can operate the proposed lever propulsion mechanism.
Inhibition of Neutrophil Adherence Improves Postischemic Ventricular Performance of the Neonatal Heart

BackgroundReduction of the leukocyte population during postischemic coronary reperfusion results in decreased neutrophil-mediated tissue injury. However, the importance of leukocyte adhesion to coronary endothelium for postischemic ventricular dysfunction after global hypothermic myocardial ischemia is unknown. Neutrophil integrins (CD11b/CD18) upregulate in response to cardiopulmonary bypass and ischemic stress, and their role in generating postoperative ventricular dysfunction was examined in this study. Methods and ResultsAn in vivo, in situ model of neonatal cardiac surgery was established in which neutrophil adherence was manipulated by administering NPC 15669 (an inhibitor of neutrophil CD11b/CD18 surface receptor upregulation). Seventeen 3- to 5-day-old piglets (8 controls and 9 NPC 15669-treated animals) were instrumented with a coronary sinus catheter, sonomicrometry crystals across the short axis of the left ventricle (LV), and a micromanometer positioned in the LV. Hearts were subjected to 90 minutes of hypothermic ischemia after a single dose of cold crystalloid cardioplegia. Myocardial granulocyte accumulation during ischemia and reperfusion was reduced in NPC animals compared with controls (myeloperoxidase activity, 43.4±2.6 and 75.8±6.3 jumol/10 mg tissue, respectively; P'.005). This was associated with a reduction in coronary vascular resistance in NPC animals compared with controls (P<.02) and decreased release of myocardial creatine phosphokinase throughout reperfusion (P<.05). NPC animals demonstrated an improved preservation of the end-systolic pressurevolume relation after discontinuation of cardiopulmonary bypass (71±6% and 96±6% at 60 minutes, respectively; Ps.05). There was no difference in ventricular compliance between groups. ConclusionsThese data demonstrate that inhibition of neutrophil CD11b/CD18 surface adherence receptor upregulation reduces granulocyte accumulation in myocardium after hypothermic global ischemia, reduces myocyte damage, and improves ventricular systolic function.
PHOTOINHIBITION OF PSII IN EMILIANIA HUXLEYI (HAPTOPHYTA) UNDER HIGH LIGHT STRESS: THE ROLES OF PHOTOACCLIMATION, PHOTOPROTECTION, AND PHOTOREPAIR 1

The response of the coccolithophorid Emiliania huxleyi (Lohmann) W. H. Hay et H. Mohler to acute exposure to high photon flux densities (PFD) was examined in terms of PSII photoinhibition, photoprotection, and photorepair. The time and light dependencies of these processes were characterized as a function of the photoacclimation state of the alga. Low‐light (LL) acclimated cells displayed a higher degree of photoinhibition, measured as decline in Fv/Fm, than high‐light (HL) acclimated cells. However, HL cultures were more susceptible to photodamage but also more capable of compensating for it by performing a faster repair cycle. The relation between gross photoinhibition (observed in the presence of an inhibitor of repair) and PFD to which the algae were exposed deviated from linearity at high PFD, which calls into question the universality of current concepts of photoinhibition in mechanistic models. The light dependence of the de‐epoxidation state (DPS) of the xanthophyll cycle (XC) pigments on the timescale of hours was the same in cells acclimated to LL and HL. However, HL cells were more efficient in realizing nonphotochemical quenching (NPQ) on short timescales, most likely due to a larger XC pool. LL cells displayed an increase in the PSII effective cross‐section (σPSII) as a result of photoinhibition, which was observed also in HL cells when net photoinhibition was induced by blocking the D1 repair cycle. The link between σPSII and photoinhibition suggests that the population of PSII reaction centers (RCIIs) of E. huxleyi shares a common antenna, according to a “lake” organization of the light‐harvesting complex.
Astrocytic activation in the anterior cingulate cortex is critical for sleep disorder under neuropathic pain

Insomnia, depression, and anxiety disorder are common problems for people with neuropathic pain. In this study, mild noxious heat stimuli increased the duration and number of spontaneous pain‐like behaviors in sciatic nerve‐ligated mice. We used functional magnetic resonance imaging to visualize the increased blood oxygenation level‐dependent signal intensity in the anterior cingulate cortex (ACC) of mice with sciatic nerve ligation under mild noxious stimuli. Such stimuli significantly increased the release of glutamate in the ACC of nerve‐ligated mice. In addition, sciatic nerve ligation and mild noxious stimuli changed the morphology of astrocytes in the ACC. Treatment of cortical astrocytes with glutamate caused astrocytic activation, as detected by a stellate morphology. Furthermore, glutamate induced the translocation of GAT‐3 to astrocyte cell membranes using primary cultured glial cells from the mouse cortex. Moreover, the GABA level at the synaptic cleft in the ACC of nerve‐ligated mice was significantly decreased exposure to mild noxious stimuli. Finally, we investigated whether astrocytic activation in the ACC could directly mediate sleep disorder. With the optogenetic tool channel rhodopsin‐2 (ChR2), we demonstrated that selective photostimulation of these astrocytes in vivo triggered sleep disturbance. Taken together, these results suggest that neuropathic pain‐like stimuli activated astrocytes in the ACC and decreased the extracellular concentration of GABA via an increase in the release of glutamate. Furthermore, these findings provide novel evidence that astrocytic activation in the ACC can mimic sleep disturbance in mice. Synapse 68:235–247, 2014. © 2014 Wiley Periodicals, Inc.
Surgical Decompression Improves Mortality and Morbidity After Large Territory Acute Cerebral Infarction: A Critically Appraised Topic

BackgroundPatients who suffer from large territory cerebral infarctions have poor prognosis. Whether adjunctive surgical therapy improves clinical outcomes has long been a controversial topic. ObjectiveTo determine whether surgical decompression, compared with best medical management, improves mortality and morbidity in the setting of a large territory acute middle cerebral artery infarction. MethodsThe objective was addressed through the development of a structured critically appraised topic. This included development of a clinical scenario, structured clinical questions, search strategy and selection of an article, critical appraisal, evidence summary, clinical bottom lines, and expert commentary from vascular neurologists and a vascular neurosurgeon. ResultsThe study selected for appraisal included data from both a multicenter randomized trial and an updated meta-analysis. Surgical decompression within 4 days of stroke onset did not reduce the risk of poor outcome [absolute risk reduction (ARR), 0%; 95% confidence interval (CI), −21% to 21%]; however, it did reduce case fatality (ARR, 38%; 95% CI, 15% to 60%). The updated meta-analysis showed that surgical decompression within 48 hours of stroke onset reduces both poor outcome [ARR, 42%; 95% CI, 23% to 56%; number needed to treat (NNT)=2; 95% CI, 2 to 4] and case fatality (ARR, 50%; 95% CI, 32% to 64%; NNT=2; 95% CI, 2 to 3). ConclusionsEarly surgical decompression (within 48 h of stroke onset) reduces the risks of death and poor clinical outcome at 1 year in patients with large territory cerebral infarction.
Puromycin-Sensitive Aminopeptidase Limits MHC Class I Presentation in Dendritic Cells but Does Not Affect CD8 T Cell Responses during Viral Infections1

Previous experiments using enzyme inhibitors, cell lysates, and purified enzyme have suggested that puromycin-sensitive aminopeptidase (PSA) plays a role in creating and destroying MHC class I-presented peptides although its precise contribution to these processes is unknown. To examine the importance of this enzyme in MHC class I Ag presentation, we have generated PSA-deficient mice and cell lines from these animals. PSA-deficient mice are smaller and do not reproduce as well as wild type mice. In addition, dendritic cells from PSA-deficient mice display more MHC class I molecules on the cell surface, suggesting that PSA normally limits Ag presentation by destroying certain peptides in these key APCs. Surprisingly, MHC class I levels are not altered on other PSA-deficient cells and the processing and presentation of peptide precursors in PSA-deficient fibroblasts is normal. Moreover, PSA-deficient mice have normal numbers of T cells in the periphery, and respond as well as wild type mice to eight epitopes from three viruses. These data indicate that PSA may play a role in limiting MHC class I Ag presentation in dendritic cells in vivo but that it is not essential for generating most MHC class I-presented peptides or for stimulating CTL responses to several Ags.
What causes mental dysfunction in Parkinson's disease?

Parkinson's disease (PD) is frequently associated with mental dysfunction. Domain‐specific cognitive deficits are ubiquitous, and although they may not be clinically apparent in all patients, they are demonstrable by neuropsychological testing. Dementia is less frequent but is present significantly more in PD patients than in controls, with a cumulative prevalence rate up to 40% and up to six‐fold increased incidence. Cognitive impairment mainly involves executive and visuospatial functions; memory is secondarily impaired with relatively preserved recognition. Qualitatively, the neuropsychological profile of dementia encompasses the same type of deficits found in nondemented PD patients. The dementia seen in PD, therefore, can be described as a dysexecutive syndrome combined with visuospatial dysfunction and behavioural symptoms. Dopaminergic, noradrenergic, serotoninergic, and cholinergic deficits have all been described as the underlying neurochemical impairment, but the strongest evidence exists for a cholinergic dysfunction. Involvement of brainstem nuclei, limbic structures, and cerebral cortex have been suggested as the site, and Lewy body (LB) degeneration and Alzheimer‐type changes as the type of pathology underlying the mental dysfunction in PD. Although there is still some controversy as to the site and type of pathology, recent evidence suggests that LB‐type degeneration in limbic structures and cerebral cortex, with consequent synaptic and cell loss, is the main pathological state associated with dementia in PD. © 2003 Movement Disorder Society
A Positive Feedback Loop between Protein Kinase CKII and Cdc37 Promotes the Activity of Multiple Protein Kinases*

We report here the identification ofCDC37, which encodes a putative Hsp90 co-chaperone, as a multicopy suppressor of a temperature-sensitive allele (cka2-13 ts) of the CKA2 gene encoding the α′ catalytic subunit of protein kinase CKII. Unlike wild-type cells, cka2-13 cells were sensitive to the Hsp90-specific inhibitor geldanamycin, and this sensitivity was suppressed by overexpression of either Hsp90 or Cdc37. However, onlyCDC37 was capable of suppressing the temperature sensitivity of a cka2-13 strain, implying that Cdc37 is the limiting component. Immunoprecipitation of metabolically labeled Cdc37 from wild-type versus cka2-13 strains revealed that Cdc37 is a physiological substrate of CKII, and Ser-14 and/or Ser-17 were identified as the most likely sites of CKII phosphorylationin vivo. A cdc37-S14,17A strain lacking these phosphorylation sites exhibited severe growth and morphological defects that were partially reversed in a cdc37-S14,17E strain. Reduced CKII activity was observed in both cdc37-S14A andcdc37-S17A mutants at 37 °C, and cdc37-S14Aor cdc37-S14,17A overexpression was incapable of protectingcka2-13 mutants on media containing geldanamycin. Additionally, CKII activity was elevated in cells arrested at the G1 and G2/M phases of the cell cycle, the same phases during which Cdc37 function is essential. Collectively, these data define a positive feedback loop between CKII and Cdc37. Additional genetic assays demonstrate that this CKII/Cdc37 interaction positively regulates the activity of multiple protein kinases in addition to CKII.
Does PET-CT scan have a role prior to radical re-resection for incidental gallbladder cancer?

BACKGROUND Radical re-resection is offered to patients with non-metastatic, invasive, incidental gallbladder cancer. Data evaluating (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in patients with incidental gallbladder cancer is sparse. AIM To evaluate the efficacy of integrated (18)F-FDG PET-CT in determining occult metastatic or residual local-regional disease in patients with incidental gallbladder cancer. METHODS Patients referred with incidental gallbladder cancer for radical re-resection were evaluated using multidetector computed tomography (MDCT) and PET-CT. Based on preoperative imaging, 24 out of 92 patients were found suitable for surgery. The two imaging modalities were evaluated with respect to residual and resectable disease. RESULTS In determining residual disease, MDCT had a sensitivity and positive predictive value (PPV) of 42.8%, each, while PET-CT had a sensitivity and PPV of 28.5 and 20%, respectively. In determining resectability, MDCT had a sensitivity, PPV, and accuracy of 100, 87.5, and 87.5%, respectively, as compared to PET-CT (sensitivity=100%, PPV=91.3%, accuracy=91.6%). CONCLUSIONS From our study, it appears that in patients with incidental gall bladder cancer without metastatic disease, PET-CT and MDCT seem to have roles complementing each other. PET-CT was able to detect occult metastatic or residual local-regional disease in some of these patients, and seems to be useful in the preoperative diagnostic algorithm of patients whose MDCT is normal or indicates locally advanced disease.
Reprogramming Tumor-Infiltrating Dendritic Cells for CD103+CD8+ Mucosal T-cell Differentiation and Breast Cancer Rejection

Wu and colleagues show that intratumoral delivery of dectin-1 ligand curdlan in a humanized mouse model of breast cancer reprograms dendritic cells to induce Th1 cytokine production as well as expansion and accumulation of CD103+CD8+ mucosal T cells in tumors, leading to cancer rejection. Our studies showed that tumor-infiltrating dendritic cells (DC) in breast cancer drive inflammatory Th2 (iTh2) cells and protumor inflammation. Here, we show that intratumoral delivery of the β-glucan curdlan, a ligand of dectin-1, blocks the generation of iTh2 cells and prevents breast cancer progression in vivo. Curdlan reprograms tumor-infiltrating DCs via the ligation of dectin-1, enabling the DCs to become resistant to cancer-derived thymic stromal lymphopoietin (TSLP), to produce IL-12p70, and to favor the generation of Th1 cells. DCs activated via dectin-1, but not those activated with TLR-7/8 ligand or poly I:C, induce CD8+ T cells to express CD103 (αE integrin), a ligand for cancer cells, E-cadherin. Generation of these mucosal CD8+ T cells is regulated by DC-derived integrin αvβ8 and TGF-β activation in a dectin-1–dependent fashion. These CD103+CD8+ mucosal T cells accumulate in the tumors, thereby increasing cancer necrosis and inhibiting cancer progression in vivo in a humanized mouse model of breast cancer. Importantly, CD103+CD8+ mucosal T cells elicited by reprogrammed DCs can reject established cancer. Thus, reprogramming tumor-infiltrating DCs represents a new strategy for cancer rejection. Cancer Immunol Res; 2(5); 487–500. ©2014 AACR.
Projected Nesterov's proximal-gradient signal recovery from compressive poisson measurements

We develop a projected Nesterov's proximal-gradient (PNPG) scheme for reconstructing sparse signals from compressive Poisson-distributed measurements with the mean signal intensity that follows an affine model with known intercept. The objective function to be minimized is a sum of convex data fidelity (negative log-likelihood (NLL)) and regularization terms. We apply sparse signal regularization where the signal belongs to a closed convex set within the domain of the NLL and signal sparsity is imposed using total-variation (TV) penalty. We present analytical upper bounds on the regularization tuning constant. The proposed PNPG method employs projected Nesterov's acceleration step, function restart, and an adaptive step-size selection scheme that aims at obtaining a good local majorizing function of the N LL and reducing the time spent backtracking. We establish O (k-2) convergence of the PNPG method with step-size backtracking only and no restart. Numerical examples demonstrate the performance of the PNPG method.
Clinical management and humoral immune responses to rabies post‐exposure prophylaxis among three patients who received solid organs from a donor with rabies

The rabies virus causes a fatal encephalitis and can be transmitted through organ transplantation. In 2013, a man developed rabies 18 months after receiving a kidney from a donor with rabies, who was not known to have been infected when the organs were procured. Three additional persons who received organs from the same donor (liver, kidney, heart), all of whom were not vaccinated for rabies before transplantation, received rabies post‐exposure prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as soon as the diagnosis of rabies was made in the donor (18 months after their transplant surgeries). We describe their clinical management.