Caffeine-Operated Synthetic Modules for Chemogenetic Control of Protein Activities by Life Style.
A genetically encoded caffeine-operated synthetic module (COSMO) is introduced herein as a robust chemically induced dimerization (CID) system. COSMO enables chemogenetic manipulation of biological processes by caffeine and its metabolites, as well as caffeinated beverages, including coffee, tea, soda, and energy drinks. This CID tool, evolved from an anti-caffeine nanobody via cell-based high-throughput screening, permits caffeine-inducible gating of calcium channels, tumor killing via necroptosis, growth factors-independent activation of tyrosine receptor kinase signaling, and enhancement of nanobody-mediated antigen recognition for the severe acute respiratory distress coronavirus 2 (SARS-CoV-2) spike protein. Further rationalized engineering of COSMO leads to 34-217-fold enhancement in caffeine sensitivity (EC50 = 16.9 nanomolar), which makes it among the most potent CID systems like the FK506 binding protein (FKBP)-FKBP rapamycin binding domain (FRB)-rapamycin complex. Furthermore, bivalent COSMO (biCOMSO) connected with a long linker favors intramolecular dimerization and acts as a versatile precision switch when inserted in host proteins to achieve tailored function. Given the modularity and high transferability of COMSO and biCOSMO, these chemical biology tools are anticipated to greatly accelerate the development of therapeutic cells and biologics that can be switched on and off by caffeinated beverages commonly consumed in the daily life.


Prediction of hemorrhagic transformation following acute stroke: role of diffusion- and perfusion-weighted magnetic resonance imaging.
Acute diffusion-weighted (DWI) and perfusion-weighted (PWI) magnetic resonance imaging (MRI) findings may correlate with secondary hemorrhagic transformation (HT) risk in patients with stroke. This information could be of value, particularly in individuals being considered for thrombolytic therapy. To determine the relationship between DWI and PWI findings and the risk of secondary HT in patients with acute stroke. Retrospective case series. Academic medical center. Twenty-seven patients with acute stroke capable of being evaluated with DWI/PWI 8 hours or less after symptom onset. Apparent diffusion coefficient values, perfusion delay measurements, and subsequent MRI or computed tomographic scans detected HT. The mean +/- SD apparent diffusion coefficient of ischemic regions that experienced HT was significantly lower than the overall mean +/- SD apparent diffusion coefficient of all ischemic areas analyzed (0.510 +/- 0.140 x 10(-3) mm(2)/s vs 623 +/- 0.113 x 10(-3) mm(2)/s; P =.004). This difference remained significant when comparing the HT-destined ischemic areas with the non-HT-destined areas within the same ischemic lesion (P =.02). Patients receiving recombinant tissue-type plasminogen activator (rt-PA) experienced HT significantly earlier than patients not receiving rt-PA (P =.002). Moreover, a persistent perfusion deficit in the area of subsequent hemorrhage at 3 to 6 hours after the initial MRI scan was identified in significantly more patients who experienced HT than in those who did not (83% vs 30%; P =.03). Both DWI and PWI scans detect abnormalities that are associated with HT. These findings support a role for MRI in identifying patients who are at increased risk for secondary HT following acute ischemic stroke.


Independent predictors of shunt-dependent normal pressure hydrocephalus after aneurysmal subarachnoid hemorrhage.
Normal pressure hydrocephalus frequently develops after subarachnoid hemorrhage. It can often be difficult, however, to predict shunt dependency. The purpose of this study was to identify predictors of shunt-dependent normal pressure hydrocephalus (SDNPH) after aneurysmal subarachnoid hemorrhage (aSAH). The incidence of SDNPH in 139 consecutive patients who underwent surgery for aSAH in the Department of Neurosurgery Tokyo Medical and Dental University between January 2008 and December 2011 was evaluated. The patientage, Glasgow Coma Score, World Federation of Neurosurgical Societies grade, Hunt and Hess grade, modified Fisher group, modified Rankin Scale, duration of external drainage of cerebrospinal fluid (CSF), gender, aneurysm location, presence of intraventricular hemorrhage, surgical method (clip or coil), and presence of acute hydrocephalus were analyzed. Forty-seven of 139 patients (33.8%) underwent shunt operation. Fifteen of these 47 patients were assessed to have high-pressure hydrocephalus and excluded. Thirty-two SDNPH patients (23.0%) were compared with 84 patients without hydrocephalus (60.4%). An age of 65 years or over (OR 5.51;95%CI 1.97-15.40), a GCS of 13 or less (OR 3.82;95%CI 1.38-10.60), and CSF drainage for a duration of 12 days or more (OR 3.63;95%CI 1.30-10.14) were independently associated with SDNPH. SDNPH after aSAH in our study showed no correlations with three of the parameters previously identified as risk factors for shunt-dependent hydrocephalus, namely, the amount of SAH, the presence of IVH, or acute hydrocephalus. Instead, a longer duration of CSF drainage correlated with SDNPH as an independent factor. These data suggest that a longer duration of CSF drainage may be one of the risk factors for SDNPH after aSAH.


Relating the marginal fit of the castings to the accuracy of the impressions made from laminated hydrocolloid impression technique: a comparative study.
Relating the marginal fit of the castings, to the accuracy of the impression produced using laminated hydrocolloid impression technique, alginate and double-mixed polyvinyl siloxane. Basic objective of the study is to check the feasibility of the use of laminated hydrocolloid impression technique in the fixed partial denture. The precisely machined metal die was designed to simulate standard complete metal crown preparation. The preparation was mounted on cylindrical base of 20 mm length and diameter of 10 mm. Seven impressions were made from the each impression material onto the metal die, and total 21 impressions were obtained from all three impression materials, which were poured by the die stone, and stone die was prepared. Wax patterns were fabricated on stone dies obtained from each impression and then casting was done. All the castings were checked for the marginal fit on metal die after applying a uniform standardized load of 30 pounds using measuring microscope. Result revealed that the marginal fit of the castings obtained from group II (laminated hydrocolloid technique) and group III (double-mix polyvinyl polysiloxane) did not show the significant difference between the two of them. Marginal gap of the castings obtained from group I are significantly greater in comparison to the castings obtained from groups II and III (p > 0.01). Group II (laminated hydrocolloid technique) impression material may be the choice of many clinicians over group III (double-mix polyvinyl polysiloxane) impression material. Group I (alginate impression material), though very cost-effective and easy to handle may not able to produce accurate results. The study gives overview of the best impression material that can be used clinically. Laminated hydrocolloid technique is the technique of choice.


[Clinical study of non-melanoma skin cancer following human organ transplantation].
Increasing evidence suggests that non-melanoma skin cancers (NMSC) are the most frequent tumours in transplanted patients. In this study, we present the first Hungarian dermatological screening program to establish the incidence of NMSC after organ transplantations. 116 adult, "Caucasian" (white skin) transplanted (kidney, simultaneous-pancreas-kidney) patients (70 male and 46 female) of the Surgical Department of Pécs University were enrolled from September 2008. All patients underwent a a full skin examination by a dermatologist for NMSC as well as a standardized questionnaire was filled in to assess risk factors. Screening resulted in 16 NMSC (13.8%, median age: 49.3 years, male : female = 1 : 1) diagnoses with a median duration from transplantation of 4.1 years. Histology showed 13 basal cell carcinoma (BBC), 3 squamous cell carcinoma (SCC), with a 4 : 1 ratio of BCC : SCC. Incidence of NMSC was significantly higher on patients who were treated with cyclosporine as immunosuppressant, who had more than 2 sunburns prior to transplantation, or had outdoor workplace ( p < 0.05). These data confirm the importance of skin cancer surveillance in transplant recipients via a close cooperation between Transplantation and Dermatological Centres. Our results reflect the international data, except for the BCC : SCC ratio. Further studies needed to elucidate this difference.


[Ruptures of the anterior cruciate ligament (ACL) during growth].
Tears of the anterior cruciate ligament (ACL) in skeletally immature patients with open physes are becoming more frequent. The two main variants of this lesion include tibial eminence fractures with an avulsion of the bony avulsions of the ACL on the tibia and midsubstance ligament injuries. The treatment of bony avulsions is generally accepted. In complete midsubstance tears conservative treatment is insufficient, resulting in multiple giving way episodes and meniscal lesions. Controversy exists regarding the surgical treatment of complete midsubstance ruptures. Especially in younger patients with wide open physes, the risk of a growth disturbance due to transphyseal drilling has not been completely evaluated. In patients approaching physeal closure intraarticular ACL replacement using an autogenous bone-patellar tendon-bone graft has been shown to yield good short-term to mid-term results. There is a growing concern regarding the long-term outcome of ACL grafts with higher rerupture rates being suspected in children compared to adults. For these reasons more clinical and experimental data are needed in forthcoming studies.


Delayed Post-Surgical Hypoparathyroidism: The Forgotten Chameleon!
Delayed hypoparathyroidism, due to accidental gland removal or ischemia of parathyroids can present many years after thyroidectomy and symptoms may be non-specific. This condition, if not diagnosed timely, may prove fatal and have serious consequences. Hence, clinicians must have a high index of suspicion to treat this condition. All patients with a history of previous thyroid surgery, who come with vague symptoms like fatigue, muscle aches should undergo estimation of serum calcium, phosphorus and Parathyroid Hormone (PTH) due to the lack of any pathognomonic features of hypoparathyroidism. We report a rare case of delayed post-surgical hypoparathyroidism who became symptomatic 15 years after thyroid surgery and remained so for another 10 years before the final diagnosis was established.


Hand impairment in systemic sclerosis: association of different hand indices with organ involvement.
To evaluate the association between the assessment tools used to quantify hand impairment and organ involvement in patients with systemic sclerosis (SSc). Eighty consecutive SSc patients were assessed for hand impairment using the Hand Anatomic Index (HAI), finger-to-palm distance in flexion (FTP), and the Hand Mobility in Scleroderma (HAMIS) test. Cluster analysis was used to identify patients having similar characteristics on the basis of the pattern of organ involvement in order to create clinically homogeneous groups, and to correlate these clusters with the measures of hand involvement. Finally, we evaluated the discriminating ability of the indices to identify the patients whose clinical condition was more severe. Two major clusters were identified by cluster analysis on the basis of organ involvement. The first (cluster A) included 61 patients and the second (cluster B) 19 patients characterized by minor and major extent of organ involvement, respectively. The extent of organ involvement and the hand impairment were related. The scores of hand indices were lower in cluster B. The area under the receiver operating characteristic (ROC) curve (C-index) for the logistic model including all three indices was 0.85 (95% confidence interval 0.74–0.95). The seriousness of hand involvement as measured by the three indices was associated with the extent of organ involvement. Further studies of hand impairment scales are needed to provide validated guidance as meaningful clinical measures.


Evaluation of the cationic trypsinogen gene for potential mutations in miniature schnauzers with pancreatitis.
The purpose of this study was to evaluate the cationic trypsinogen gene in miniature schnauzers for possible mutations. Genetic mutations have been linked with hereditary pancreatitis in humans. Four miniature schnauzers were selected on the basis of a clinical history of pancreatitis. One healthy miniature schnauzer and 1 healthy mixed breed canine were enrolled as controls. DNA was extracted from these canines using a commercial kit. Primers were designed to amplify the entire canine cationic trypsinogen cDNA sequence. A polymerase chain reaction (PCR) was performed and products were purified and sequenced. All sequences were then compared. The healthy control canine, a healthy miniature schnauzer, and the 4 miniature schnauzers with pancreatitis showed identical sequences of the cationic trypsinogen gene to the published sequence. We conclude that, in contrast to humans with hereditary pancreatitis, mutations of the cationic trypsinogen gene do not play a major role in the genesis of pancreatitis in the miniature schnauzer.


Modulation of glycosylation and transport of viral membrane glycoproteins by a sodium ionophore.
Analysis of viral glycoprotein expression on surfaces of monensin-treated cells using a fluorescence-activated cell sorter (FACS) demonstrated that the sodium ionophore completely inhibited the appearance of the vesicular stomatitis virus (VSV) G protein on (Madin-Darby canine kidney) MDCK cell surfaces. In contrast, the expression of the influenza virus hemagglutinin (HA) glycoprotein on the surfaces of MDCK cells was observed to occur at high levels, and the time course of its appearance was not altered by the ionophore. Viral protein synthesis was not inhibited by monensin in either VSV- or influenza virus-infected cells. However, the electrophoretic mobilities of viral glycoproteins were altered, and analysis of pronase-derived glycopeptides by gel filtration indicated that the addition of sialic acid residues to the VSV G protein was impaired in monensin-treated cells. Reduced incorporation of fucose and galactose into influenza virus HA was observed in the presence of the ionophore, but the incompletely processed HA protein was cleaved, transported to the cell surface, and incorporated into budding virus particles. In contrast to the differential effects of monensin on VSV and influenza virus replication previously observed in monolayer cultures of MDCK cells, yields of both viruses were found to be significantly reduced by high concentrations of monensin in suspension cultures, indicating that cellular architecture may play a role in determining the sensitivity of virus replication to the drug. Nigericin, an ionophore that facilitates transport of potassium ions across membranes, blocked the replication of both influenza virus and VSV in MDCK cell monolayers, indicating that the ion specificity of ionophores influences their effect on the replication of enveloped viruses.


Inward H+ pump xenorhodopsin: Mechanism and alternative optogenetic approach.
Generation of an electrochemical proton gradient is the first step of cell bioenergetics. In prokaryotes, the gradient is created by outward membrane protein proton pumps. Inward plasma membrane native proton pumps are yet unknown. We describe comprehensive functional studies of the representatives of the yet noncharacterized xenorhodopsins from Nanohaloarchaea family of microbial rhodopsins. They are inward proton pumps as we demonstrate in model membrane systems, Escherichia coli cells, human embryonic kidney cells, neuroblastoma cells, and rat hippocampal neuronal cells. We also solved the structure of a xenorhodopsin from the nanohalosarchaeon Nanosalina (NsXeR) and suggest a mechanism of inward proton pumping. We demonstrate that the NsXeR is a powerful pump, which is able to elicit action potentials in rat hippocampal neuronal cells up to their maximal intrinsic firing frequency. Hence, inwardly directed proton pumps are suitable for light-induced remote control of neurons, and they are an alternative to the well-known cation-selective channelrhodopsins.


Oxygen requirement of bicarbonate-dependent sodium reabsorption in the dog kidney.
The ratio between changes in sodium reabsorption and renal oxygen consumption (Na/O2) was measured in anesthetized dogs at high plasma bicarbonate concentration (32 +/- 1 mM); ethacrynic acid was infused continuously to prevent variations in transcellular NaCl reabsorption when sodium reabsorption was altered by varying plasma PCO2 and glomerular filtration rate (GFR). At high plasma PCO2 (110 mmHg) sodium reabsorption varied in proportion to GRF between 50 and 125% of control GFR (glomerulotubular balance). By reducing PCO2 to 20 mmHg, sodium reabsorption was reduced by 50-60% at constant GFR. The Na/O2 ratio was not significantly different during the two procedures and averaged 48 +/- 2. The ratio between changes in NaHCO3 reabsorption and oxygen consumption averaged 17 +/- 1, which is not significantly different from the Na/O2 ratio of Na-K-ATPase-dependent sodium transport. We propose that NaHCO3 is admitted to the cell by Na+/H+ exchange and that sodium is actively transported by Na-K-ATPase across the peritubular cell membrane; NaHCO3 provides the osmotic force for paracellular reabsorption of water and NaCl (bicarbonate-dependent reabsorption) without additional energy requirement.


[Organization of cardiologic rehabilitation in central Europe: retrospect, present, future outlook].
Cardiological rehabilitation, the comprehensive efficient treatment of chronic cardiac patients, is presented with regard to its difficult theoretical and practical development from the viewpoint of a senior specialist in this field practising in Central Europe. The accompanying WHO lifestyle concept is now considered to be scientifically well-founded, but has not yet been practically implemented on a large scale nor incorporated in the teaching schedule. A requirement for the future is a special medical philosophy for chronic heart patients, i.e., further development of the theoretical basis of rehabilitation, practical application of the scientific recommendations on the importance of life-style alterations, a greatly improved network of all doctors treating chronic heart patients, updating of the training of general medical specialists as well as cardiologists in Public Health, and intensified objective assessment of research on the cardiological rehabilitation of in- and outpatients.


[Mouthwash solutions containing microencapsuled natural extracts: In vitro evaluation of antioxidant properties (dental plaque and gingivitis)].
New mouthwash solutions containing microencapsulated natural extracts were developed to provide both antiseptic activity and in depth treatment of oral tissues, due to their antioxidant and immunoregulatory properties. The objective of this study was to quantify the antioxidant action of the GingiNat solution (LoB5 Foundation, Paris, France) in an in vitro cell model. Diluted GingNat solutions (0.12%, 0.06% and 0.012%) were put in contact with Jurkat type human lymphoid cells in basal radical state (cells at rest) and in provoked oxidative stress conditions (after an UVA+UVB irradiation). The lipid peroxidation was quantified by flow cytometry using a fluorescent probe. The diluted GingNat solutions at 0.12%, 0.06%, and 0.012% showed a significant antioxidant effect with respectively 122.9%, 117.8% and 119.3% on average. The difference was statistically significant compared to controls for the three concentrations without any significant difference among them. This antioxidant effect was even more significant when cells were in oxidative stress with respectively 155.3%, 139.3%, and 132.5% on average. There was a significant difference between the tested concentrations (p<0.01). These first in vitro results confirmed the antioxidant properties of the GingiNat solution. These antioxidant properties are significantly higher at stronger concentrations. Further studies are required to analyze the influence of microencapsulation on these results. Clinical trials are needed to confirm these antioxidant properties.


The Food Stamp Program and Supplemental Security Income.
The Food Stamp Program (FSP) and Supplemental Security Income (SSI) are important parts of national public assistance policy, and there is considerable overlap in the populations that the programs serve. About half of all SSI recipients reside in FSP recipient households. This article uses Social Security administrative data and the Food Stamp Quality Control samples for federal fiscal years 2001-2006 to study the prevalence of food stamp receipt among households with SSI recipients, the contribution of FSP to household income, and the importance of various FSP features in contributing to the well-being of recipient households. The prevalence of FSP participation among households that include SSI recipients is estimated to have grown steadily over the entire 2001-2006 period, rising from 47.4 percent in 2001 to 55.6 percent in 2006. This growth has occurred across all age groups of SSI recipients. The FSP contribution to household income has grown as well. In 2001, FSP increased the income of the households of SSI/FSP recipients by 13 percent; by 2006 the increase was 16.8 percent. Almost 80 percent of the food stamp recipient households that include SSI recipients receive increased benefits because of excess housing costs. In 2006, 44 percent of SSI recipients lived in households that did not receive food stamps. Given available information, it is difficult to gauge the FSP eligibility of nonparticipating households and, therefore, to assess the potential benefit of outreach efforts. Currently available measures of FSP take-up probably overstate participation among eligible households that include SSI recipients, and there is some evidence that enhanced state promotion of the FSP raises participation among households with SSI recipients. We conclude with recommendation for review and renewal of collaboration between the Food and Nutrition Service of the U.S. Department of Agriculture (the agency responsible for administering the FSP) and the Social Security Administration in ensuring that eligible SSI recipients utilize FSP benefits.


Air pollution monitoring by advanced spectroscopic techniques.
The monitoring requirements related to air pollution are many and varied. The molecules of concern differ greatly in their chemical and physical properties, in the nature of their environment, and in their concentration ranges. Furthermore, the application may have specific requirements such as rapid response time, ultrasensitivity, multipollutant capability, or capability for remote measurements. For these reasons, no single spectroscopic technique appears to offer a panacea for all monitoring needs. Instead we have attempted to demonstrate in the above discussion that, regardless of the difficulty and complexity of the monitoring problems, spectroscopy offers many tools by which such problems may be solved.


Candidate prioritization for low-abundant differentially expressed proteins in 2D-DIGE datasets.
Two-dimensional differential gel electrophoresis (2D-DIGE) provides a powerful technique to separate proteins on their isoelectric point and apparent molecular mass and quantify changes in protein expression. Abundantly available proteins in spots can be identified using mass spectrometry-based approaches. However, identification is often not possible for low-abundant proteins. We present a novel computational approach to prioritize candidate proteins for unidentified spots. Our approach exploits noisy information on the isoelectric point and apparent molecular mass of a protein spot in combination with functional similarities of candidate proteins to already identified proteins to select and rank candidates. We evaluated our method on a 2D-DIGE dataset comparing protein expression in uninfected and HIV-1 infected T-cells. Using leave-one-out cross-validation, we show that the true-positive rate for the top-5 ranked proteins is 43.8%. Our approach shows good performance on a 2D-DIGE dataset comparing protein expression in uninfected and HIV-1 infected T-cells. We expect our method to be highly useful in (re-)mining other 2D-DIGE experiments in which especially the low-abundant protein spots remain to be identified.


Outcome of first-ever acute ischemic stroke in the elderly.
Our purpose was to evaluate the outcome of patients aged 70 years or older with a first-ever acute ischemic stroke and to identify the factors which determine poor outcome. Data from 115 patients, non-disabled prior to stroke, consecutively admitted to a medical department of a teaching hospital over a 30-month period, were prospectively collected at stroke onset and 6-month follow-up. Clinical and brain imaging findings and functional status were recorded. Predictors of unfavorable outcome at 6 months, defined as a modified Rankin Scale score >2, were analyzed by multiple logistic regression. The mean age of this cohort was 78.6 years (SD, 5.7) and 66.1% were women, 73.9% had hypertension, 25.2% diabetes, 36.0% atrial fibrillation (AF), 33.9% heart failure (HF), 15.8% previous transient ischemic attack (TIA), 47.8% a Charlson comorbidity index (CCI) score >1 and 52.2% a baseline National Institute of Health stroke scale (NIHSS) score ≥ 6. At 6 months, 54 patients (47%) had unfavorable outcome and the independent predictors of poor outcome were the initial systolic blood pressure and the NIHSS score on admission. In conclusion, near 50% of these old patients were dependent or dead 6 months after stroke onset and the main predictor of poor outcome was the neurological severity of stroke.


Abnormal findings on knee magnetic resonance imaging in asymptomatic NBA players.
The purpose of this study was to evaluate the knees of asymptomatic National Basketball Association (NBA) players via magnetic resonance imaging (MRI) and confirm or dispute findings reported in the previous literature. It is thought that a variety of significant abnormalities affecting the knee exist in asymptomatic patients and that these findings can be accurately identified on MRI. Two months prior to the 2005 season, bilateral knee MRI examinations of 14 asymptomatic NBA players (28 knees) were evaluated for abnormalities of the articular cartilage, menisci, and patellar and quadriceps tendons. The presence of joint effusion, subchondral edema, and cystic lesions and the integrity of the collateral and cruciate ligaments were also assessed.


Production of a photohexapeptide library from entomopathogenic Photorhabdus asymbiotica PB68.1.
A new natural product compound library, photohexapeptide library, was identified from entomopathogenic Photorhabdus asymbiotica PB68.1 after the NRPS-encoding gene phpS was activated via promoter exchange. Peptide structures, including the absolute configurations of amino acids, were determined by using a combination of bioinformatics analysis and isotopic labelling experiments followed by detailed HPLC-MS analysis. Additionally, their structures were confirmed by chemical synthesis and NMR after preparative isolation. The chemical diversity of the photohexapeptides results from promiscuous adenylation domain specificity being an excellent example of how to create libraries in nature.


Human neutrophils release the Leu-8 lymph node homing receptor during cell activation.
The Leu-8 molecule, the human homologue of the murine MEL-14 peripheral lymph node homing receptor, is expressed on neutrophils in both species and may be important in localization of cells to sites of inflammation. Most circulating human neutrophils express the Leu-8 molecule, and activation of neutrophils with phorbol myristate acetate causes a rapid decline in Leu-8 membrane fluorescence staining within 15 minutes. Northern blot analysis of total cellular RNA from neutrophils demonstrated two species of Leu-8 messenger RNA, a major one of 2.4 kb and a minor one of 1.9 kb. Because two different Leu-8 cDNA clones were obtained from human lymphocytes that were predicted to encode both transmembrane and phosphatidylinositol (PI)-anchored forms of the molecule, experiments were conducted to determine whether Leu-8 is anchored to neutrophils by a PI-anchor. There was a slight decrease in expression of Leu-8 on neutrophils when they were treated with PI-specific phospholipase C (PI-PLC). However, Leu-8 was abundant on neutrophils obtained from a patient with paroxysmal nocturnal hemoglobinuria. To determine the fate of the Leu-8 molecule during cell activation, neutrophils were labeled with 125I-anti-Leu-8. During activation antibody was rapidly lost from the cell surface and was not internalized, suggesting that Leu-8 is released from the cell membrane during cell activation. When cell extracts of neutrophils were compared with extracts of lymphoid cells by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting, the Leu-8 species expressed on neutrophils had a significantly higher and more variable relative mobility (70 to 120 Kd for neutrophils v 70 Kd for Jurkat T cells). In addition, Leu-8 molecules were detected in the supernatants of activated neutrophils. These results indicate that human neutrophils express a high-molecular-weight form of the Leu-8 molecule that has a conventional transmembrane anchor and is rapidly released from the membrane during activation. The loss of the Leu-8 membrane glycoprotein during activation may be a mechanism for rapid alteration of neutrophil adhesion characteristics.


H(infinity) tracking-based sliding mode control for uncertain nonlinear systems via an adaptive fuzzy-neural approach.
A novel adaptive fuzzy-neural sliding-mode controller with H(infinity) tracking performance for uncertain nonlinear systems is proposed to attenuate the effects caused by unmodeled dynamics, disturbances and approximate errors. Because of the advantages of fuzzy-neural systems, which can uniformly approximate nonlinear continuous functions to arbitrary accuracy, adaptive fuzzy-neural control theory is then employed to derive the update laws for approximating the uncertain nonlinear functions of the dynamical system. Furthermore, the H(infinity) tracking design technique and the sliding-mode control method are incorporated into the adaptive fuzzy-neural control scheme so that the derived controller is robust with respect to unmodeled dynamics, disturbances and approximate errors. Compared with conventional methods, the proposed approach not only assures closed-loop stability, but also guarantees an H(infinity) tracking performance for the overall system based on a much relaxed assumption without prior knowledge on the upper bound of the lumped uncertainties. Simulation results have demonstrated that the effect of the lumped uncertainties on tracking error is efficiently attenuated, and chattering of the control input is significantly reduced by using the proposed approach.


BET 1: Prehospital cardiac troponin testing to 'rule out' acute coronary syndromes using point of care assays.
A shortcut review of the literature was carried out to establish whether prehospital point of care (POC) troponin tests are reliable and accurate enough to detect acute coronary syndrome (ACS) in adult patients.Nine papers were found to be relevant to the clinical question following the below-described search strategies. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of those best papers are tabulated. It is concluded that based on the currently available evidence, POC troponin assays are insufficiently sensitive to 'rule out' ACS in the prehospital environment.


Effect of systemic nitroglycerin on CGRP and 5-HT afferents to rat caudal spinal trigeminal nucleus and its modulation by estrogen.
Systemic administration of nitroglycerin, a nitric oxide donor, triggers in migraine patients a delayed attack of unknown mechanism. After puberty migraine is more prevalent in women. Attacks can be triggered by abrupt falls in plasma estrogen levels, which accounts in part for sexual dimorphism, but lacks an established neurobiological explanation. We studied the effect of nitroglycerin on the innervated area of calcitonin gene-related peptide (CGRP) and serotonin-immunoreactive afferents to the superficial laminae of the spinal portion of trigeminal nucleus caudalis, and its modulation by estrogen. In male rats, nitroglycerin produced after 4 h a significant decrease of the area innervated by CGRP-immunoreactive afferents and an increase of that covered by serotonin-immunoreactive fibres. These effects were not observed in the superficial laminae of thoracic dorsal horns. The effect of nitroglycerin was similar in ovariectomized females. In estradiol-treated ovariectomized females the area in the spinal portion of trigeminal nucleus caudalis laminae I-II covered by CGRP-immunoreactive fibres was lower and that of serotonin-immunoreactive fibres was higher than in males and for both transmitters not significantly changed after nitroglycerin. The bouton size of CGRP profiles was smaller in estradiol-treated ovariectomized females, whereas after nitroglycerin it decreased significantly but only in males and ovariectomized females. Nitroglycerin, i.e. nitric oxide, is thus able to differentially influence afferent fibres in the superficial laminae of rat spinal trigeminal nucleus caudalis. Estradiol modulates the basal expression of these transmitters and blocks the nitroglycerin effect. These data may contribute to understanding the mechanisms by which estrogens influence migraine severity and the triggering of attacks by nitric oxide.


Macro and Trace Elements in Hemp (Cannabis sativa L.) Cultivated in Greece: Risk Assessment of Toxic Elements.
The accumulation of hazardous contaminants in Cannabis sativa L. raises warning signs regarding possible adverse effects on human health due to the consumption of herbal medicines and/or other herbal edible products made from cannabis. Thus, there is an urge to investigate the levels of hazardous contaminants, such as heavy metals, in cannabis plant. In the present study, 29 macro and trace elements, including both beneficial and toxic elements (heavy metals and metalloids), were investigated in 90 samples of Cannabis sativa L. collected from Greece. According to the results, the detected concentrations of macro elements in the leaves/flowers of cannabis ranged between 28 and 138,378 ppm, and of trace elements between 0.002 and 1352.904 ppm. Although the concentrations of elements varied among the samples, their accumulation pattern was found to be similar, with the contribution of toxic elements to the total concentration of trace elements being below 1%. The detected levels of the most toxic elements were below the prescribed limits established by the WHO, while the calculated THQ and CR values showed no risk (non-carcinogenic and carcinogenic) for the population exposed to the current cannabis samples. Positive correlation between the concentration of elements and cannabis geographical origin and variety was observed. Cannabis leaves/flowers were more contaminated with trace and macro elements than seeds.


What influences diagnostic delay in low-income women with breast cancer?
Delayed diagnosis of breast cancer (BC) may contribute to adverse outcomes, such as reduced survival. The purpose of this study was to identify correlates of elapsed time between recognition of breast abnormalities and receipt of definitive diagnosis of BC among low-income women. Data were obtained from a cross-sectional study among a statewide sample of 921 low-income women with a new diagnosis of BC. Patients were grouped by whether their breast abnormalities were self-detected or healthcare system detected. Multivariate logistic regression analyses were used to examine associations between diagnostic delay and patient characteristics, patient communication, and system characteristics. The self-detected group experienced much greater delay than the system-detected group (median intervals 80.5 vs. 31.5 days). African Americans had the longest intervals between symptom detection and diagnostic resolution; median delays in the self-detected and system-detected subgroups were 115 and 70 days, respectively, compared to 64 and 22 days for Caucasians. In multivariate analyses, African Americans had considerably greater odds of >60-day delay than Caucasians in both the self-detected (odds ratio [OR] 3.51) and system-detected (OR 5.36) groups. Greater perceived self-efficacy in interacting with healthcare providers was significantly associated with shorter delay among the self-detected group (OR 0.86). Disparities in timely BC diagnosis between African Americans and Caucasians were pronounced in this uniformly low-income population of women. Women with self-detected abnormalities had markedly greater delays than those with healthcare system-detected abnormalities. Among this vulnerable group, increasing self-efficacy in interacting with healthcare providers may reduce diagnostic delays.


State anxiety and depression as factors modulating and influencing postoperative pain in dental implant surgery. A prospective clinical survey.
To determine whether preoperative state anxiety and depression modulate or influence objective and subjective postoperative pain following dental implant insertion. Prospective, clinical study with 7-day follow-up of a sample of 105 subjects who preoperatively completed the state anxiety questionnaire (STAI-E) and Beck Depression Inventory (BDI) and postoperatively, at 2 and 7 days, recorded objective pain with the Semmes-Weinstein mechanical esthesiometer (SW test) and subjective pain with the Visual Analog Scale (VAS). 85.6% and 81.5% of patients, respectively, recorded no signs of state anxiety or depression. The correlation between anxiety and depression for both maxillary bones was the lower (P=0.02). The correlation between subjective and objective pain at 2 and 7 days, and the anatomic regions intervened, was statistically significant in the mandible at day 7 (P<0.01), and highly significant (P<0.001) for the other variables. The correlation between state anxiety and objective pain at day 7 was nearly statistically significant (P=0.07). The correlation between state anxiety and depression, and objective and subjective pain at day 7 was not statistically significant. A strong correlation was found between objective and subjective pain in the immediate postoperative period.


The effect of death certification practice on recorded national asthma mortality rates.
There is a wide variation in the mortality from asthma between the countries of the European Community. Studies using a standard case history of a typical asthmatic to assess death certification practice have suggested that this variation is not related to the ways that doctors fill out death certificates. Reanalysis of the data from one of these studies suggests, however, that the way doctors certify more ambivalent case histories may explain much more of the variation. Repetition of this study in a small group of French and English doctors with a special interest in asthma came to the same conclusion, suggesting that these differences are due to both a genuine difference in nosology between the countries as well as to the quality of death certification.


Rhinovirus 3C protease suppresses apoptosis and triggers caspase-independent cell death.
Apoptosis and programmed necrosis (necroptosis) determine cell fate, and antagonize infection. Execution of these complementary death pathways involves the formation of receptor-interacting protein kinase 1 (RIPK1) containing complexes. RIPK1 binds to adaptor proteins, such as TRIF (Toll-IL-1 receptor-domain-containing-adaptor-inducing interferon-beta factor), FADD (Fas-associated-protein with death domain), NEMO (NF-κB regulatory subunit IKKγ), SQSTM1 (sequestosome 1/p62), or RIPK3 (receptor-interacting protein kinase 3), which are involved in RNA sensing, NF-κB signaling, autophagosome formation, apoptosis, and necroptosis. We report that a range of rhinoviruses impair apoptosis and necroptosis in epithelial cells late in infection. Unlike the double-strand (ds) RNA mimetic poly I:C (polyinosinic:polycytidylic acid), the exposure of dsRNA to toll-like receptor 3 (TLR3) in rhinovirus-infected cells did not lead to apoptosis execution. Accordingly, necroptosis and the production of ROS (reactive oxygen species) were not observed late in infection, when RIPK3 was absent. Instead, a virus-induced alternative necrotic cell death pathway proceeded, which led to membrane rupture, indicated by propidium iodide staining. The impairment of dsRNA-induced apoptosis late in infection was controlled by the viral 3C-protease (3Cpro), which disrupted RIPK1-TRIF/FADD /SQSTM1 immune-complexes. 3Cpro and 3C precursors were found to coimmuno-precipitate with RIPK1, cleaving the RIPK1 death-domain, and generating N-terminal RIPK1 fragments. The depletion of RIPK1 or chemical inhibition of its kinase at the N-terminus did not interfere with virus progeny formation or cell fate. The data show that rhinoviruses suppress apoptosis and necroptosis, and release progeny by an alternative cell death pathway, which is controlled by viral proteases modifying innate immune complexes.


Extended composite temporoparietal fascial flap: clinical implications for tissue engineering in mandibular reconstruction.
The authors have expanded upon a well-described and widely used flap in the head and neck region. The purpose of the cadaver study was to determine the feasibility, angiosome, and the potential application of this pedicled flap in bone tissue engineering of the mandible. A total of 6 fresh human cadaver heads were dissected for a total of 12 flaps. The extended composite temporoparietal fascial flap, based on the superficial temporal artery (STA) and including cranial periosteum, was dissected and the dimensions were measured. Through a combined submandibular and preauricular incision, the mandible was exposed and the dimensions were measured from the sigmoid notch to the gonion angle and from the gonion angle to the symphysis. CT angiography and silicone injections were performed to identify the vascular anatomy of the flap. The combined distance from the sigmoid notch to the gonion and the gonion to the symphysis, plotted versus the cranial apex to tragus length, demonstrated adequate flap dimensions in all specimens for hemi-mandibular reconstruction. The average flap length was 16.5 ± 1.40 cm and the average flap width was 11.4 ± 0.98 cm, resulting in an average flap surface area of 94.5 ± 13.08 cm. Radiographic images and silicone injections confirmed STA perfusion of the cranial periosteum. The extended composite temporoparietal fascial flap with periosteum can be a viable option for providing vascularized periosteum in tissue-engineered craniofacial reconstruction.


Characterization of the interaction between zyxin and members of the Ena/vasodilator-stimulated phosphoprotein family of proteins.
Zyxin contains a proline-rich N-terminal domain that is similar to the C-terminal domain in the ActA protein of the bacteria, Listeria monocytogenes. We screened the entire amino acid sequence of human zyxin for Mena-interacting peptides and found that, as with ActA, proline-rich sequences were the sole zyxin sequences capable of binding to Ena/vasodilator-stimulated phosphoprotein (VASP) family members in vitro. From this information, we tested zyxin mutants in which the proline-rich sequences were altered. The reduction in Mena/VASP binding was confirmed by peptide tests, immunoprecipitation, and ectopic expression of zyxin variants at the surface of mitochondria. By transfection assays we showed that zyxin interaction with Mena/VASP in vivo enhances the production of actin-rich structures at the apical surface of cells. Microinjection into cells of peptides corresponding to the first proline-rich sequence of zyxin caused the loss of Mena/VASP from focal contacts. Furthermore, these peptides reduced the degree of spreading of cells replated after trypsinization. We conclude that zyxin and proteins that harbor similar proline-rich repeats contribute to the positioning of Mena/VASP proteins. The positioning of Ena/VASP family members appears to be important when the actin cytoskeleton is reorganized, such as during spreading.


Modelling of cluster emission from metal surfaces under ion impact.
Using the molecular-dynamics technique, cluster emission for 5 keV Ar bombardment of a Cu (111) surface has been investigated using a many-body (tight binding) potential for the Cu-Cu interaction. The calculations allow us to analyse the basic processes underlying cluster emission. It is found that two distinct processes can be distinguished which lead to cluster emission under energetic ion bombardment. The first process causes the emission of small clusters, which are emitted by a collective motion during the development of the collision cascade within the first picosecond after impact. Thus, emission times of such clusters agree with the emission times of atoms in sputtering. Such a process can be envisioned if, for example, a few layers below the surface, an energetic recoil causes the development of a subcascade. Energy transferred by this event to the surface is strongly directional and can lead to the simultaneous emission of a group of neighbouring surface atoms, which in some cases will remain bounded and form a cluster after emission. Typically, clusters emitted by this mechanism consist of atoms, which are neighbouring in the target and are almost exclusively surface atoms, similar to all sputtered atoms. Emission of large clusters (cluster sizes of 10 or more atoms), as observed experimentally, is a puzzling phenomenon. From our calculations we conclude that the emission of such large clusters does not occur during the collisional phase of sputtering, but happens much later (5-10 ps after ion impact). Emission can occur for spike events, where all the energy of the impinging ion is deposited locally in a small volume near to the surface, and the sputtering yield is 3-5 times the average yield. Such events are rare, but we have found a few cases in our calculations where stable clusters consisting of more than 20 atoms were emitted. Melting of the spike volume occurs, and the high temperatures and pressures produced can cause emission of large fragments during the thermal phase. The composition of such large clusters is quite different from that of small clusters. They consist of atoms from different layers and the constituents are also generally not next-neighbour atoms. This change in origin of the cluster atoms reflects the mixing and diffusion processes occurring in the melted zone before emission. The calculations indicate that hydrodynamical phenomena might play a role in the emission of large fragments. Additional calculations, where the energy was distributed 'thermally' in a three-dimensional volume under the surface for 500 fs, give very similar results, even in such cases where the kinetic phase of the collision-cascade development was absent.


Intracellular pH gradients in migrating cells.
Cell polarization along the axis of movement is required for migration. The localization of proteins and regulators of the migratory machinery to either the cell front or its rear results in a spatial asymmetry enabling cells to simultaneously coordinate cell protrusion and retraction. Protons might function as such unevenly distributed regulators as they modulate the interaction of focal adhesion proteins and components of the cytoskeleton in vitro. However, an intracellular pH (pH(i)) gradient reflecting a spatial asymmetry of protons has not been shown so far. One major regulator of pH(i), the Na(+)/H(+) exchanger NHE1, is essential for cell migration and accumulates at the cell front. Here, we test the hypothesis that the uneven distribution of NHE1 activity creates a pH(i) gradient in migrating cells. Using the pH-sensitive fluorescent dye BCECF, pH(i) was measured in five cell lines (MV3, B16V, NIH3T3, MDCK-F1, EA.hy926) along the axis of movement. Differences in pH(i) between the front and the rear end (ΔpH(i) front-rear) were present in all cell lines, and inhibition of NHE1 either with HOE642 or by absence of extracellular Na(+) caused the pH(i) gradient to flatten or disappear. In conclusion, pH(i) gradients established by NHE1 activity exist along the axis of movement.


Is that a lung edge? A case of simulated pneumothorax and survey of emergency physicians' awareness of this phenomenon.
We encountered a case whereby an 18-year-old boy presented to the Emergency Department with a stab wound to the left posterior chest. Chest X-ray (CXR) showed what appeared to be a pneumothorax and chest drain insertion was considered. It was confirmed subsequently that this apparent pneumothorax was due to a linear artefactual projection from the edge of the oxygen mask reservoir bag. We set out to investigate whether our colleagues would have misdiagnosed this artefact and what their initial treatment plan would have been. Four clinical scenarios were presented with accompanying radiographs, one of which was the case described above. Doctors were asked to examine the CXRs and accompanying scenarios, describe the radiograph findings and describe initial treatments they would perform. Twenty-three doctors (two consultants, five middle grades, and 16 senior house officers) were recruited. Two (9%) doctors indicated the 'mask sign' as a possible artefact. Nine (39%) reported the CXR as demonstrating a pneumothorax and recommended large bore chest drain insertion. Our results show that almost half of our colleagues would have carried out tube thoracostomy when no pneumothorax was actually present. In a situation where a pneumothorax is a clinical possibility we would recommend either temporarily removing the oxygen mask if clinically stable, or fixing the reservoir bag outwith the field of the CXR by means of adhesive tape to avoid any misinterpretation of this 'mask sign'.


Food preparation methods, drinking water source, and esophageal squamous cell carcinoma in the high-risk area of Golestan, Northeast Iran.
Cooking practices and water sources have been associated with an increased risk of cancer, mainly through exposure to carcinogens such as heterocyclic amines, polycyclic aromatic hydrocarbons, and nitrates. Using data from the Golestan case-control study, carried out between 2003 and 2007 in a high-risk region for esophageal squamous cell carcinoma (ESCC), we sought to investigate the association between food preparation and drinking water sources and ESCC. Information on food preparation methods, sources of drinking water, and dietary habits was gathered from 300 cases and 571 controls matched individually for age, sex, and neighborhood using a structured questionnaire and a semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounders and other known risk factors including socioeconomic status and smoking. More than 95% of the participants reported eating meat, mostly red meat. Red meat consumption above the 75th percentile increased the odds of ESCC by 2.82-fold (95% CI: 1.21-6.57). Fish intake was associated with a significant 68% decrease in ESCC odds (26%, 86%). Among meat eaters, ORs (95% CI) for frying meat (red or white) and fish were 3.34 (1.32-8.45) and 2.62 (1.24-5.5). Drinking unpiped water increased ESCC odds by 4.25 times (2.23-8.11). The OR for each 10-year increase in the duration of drinking unpiped water was 1.47 (1.22-1.78). Our results suggest roles for red meat intake, drinking water source, and food preparation methods in ESCC, even after adjusting for a large number of potential confounders.


Novel histone biotinylation marks are enriched in repeat regions and participate in repression of transcriptionally competent genes.
Covalent histone modifications play crucial roles in chromatin structure and genome stability. We previously reported biotinylation of lysine (K) residues in histones H2A, H3 and H4 by holocarboxylase synthetase and demonstrated that K12-biotinylated histone H4 (H4K12bio) is enriched in repeat regions and participates in gene repression. The biological functions of biotinylation marks other than H4K12bio are poorly understood. Here, novel biotinylation site-specific antibodies against H3K9bio, H3K18bio and H4K8bio were used in chromatin immunoprecipitation studies to obtain first insights into possible biological functions of these marks. Chromatin immunoprecipitation assays were conducted in human primary fibroblasts and Jurkat lymphoblastoma cells, and revealed that H3K9bio, H3K18bio and H4K8bio are enriched in repeat regions such as pericentromeric alpha satellite repeats and long-terminal repeats while being depleted in transcriptionally active promoters in euchromatin. Transcriptional stimulation of the repressed interleukin-2 promoter triggered a rapid depletion of histone biotinylation marks at this locus in Jurkat cells, which was paralleled by an increase in interleukin-2 mRNA. Importantly, the enrichment of H3K9bio, H3K18bio and H4K8bio at genomic loci depended on the concentration of biotin in culture media at nutritionally relevant levels, suggesting a novel mechanism of gene regulation by biotin.


Assessing the Frequency of COVID-19 in Patients Undergoing Primary Percutaneous Coronary Intervention (PCI).
The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health crisis with significant morbidity and mortality. The aim of this study was to investigate the incidence of COVID-19 in patients undergoing primary percutaneous coronary intervention (PCI) for myocardial infarction and identify associated demographic and clinical characteristics. In this study, a retrospective and descriptive cross-sectional design was used to examine all patients (a total of 85) who experienced acute myocardial infarction and underwent primary percutaneous coronary intervention (PCI). The study measured various parameters, such as COVID-19 status, age, sex, ethnicity, diabetes, and hypertension. Data analysis was conducted using SPSS version 25 software. Out of the 85 patients who underwent primary percutaneous coronary intervention (PCI) for myocardial infarction (MI), 14 patients (16.5%) were found to have COVID-19. COVID-19 diagnosis was confirmed through RT-PCR testing for 2 patients, while the remaining 12 patients were diagnosed using lung CT scans. Among the COVID-19 patients, 21.4% (n = 3) had background diabetes, and 7.1% (n = 1) had background hypertension. MI recurrence was observed in 14.3% of COVID-19 patients (2 cases). Unfortunately, 1 COVID-19 patient, a 70- year-old Persian woman with diabetes and hypertension, passed away. No significant differences were found in terms of age, sex, ethnicity, underlying diabetes, or underlying hypertension between the COVID-19 and non-COVID-19 groups. The high occurrence of COVID-19 among myocardial infarction (MI) patients undergoing primary percutaneous coronary intervention (PCI) is worth noting. Further investigation is recommended to explore the impact of demographic and contextual factors on the severity and outcomes of primary PCI in MI patients with COVID-19, as well as the underlying mechanisms involved.


Effect of ocular dominance, clinical experience, and sex on the accuracy of shade selection.
The study aimed to evaluate the influence of ocular dominance, clinical experience, and sex on the accuracy of visual color matching. A total of 104 selected participants consisting of dental students and dental practitioners were allocated into two groups based on their clinical experience of using visual shade matching tabs for the selection of tooth shade. Both the inexperienced (IXP), as well as experienced participants (EXP), were then asked to correctly match the shades of five tabs (A2, A3.5, B1, C2, and D3) of a commonly used visual shade guide (Vitapan Classical shade guide, VITA Zahnfabrik) that were kept constant throughout the study. The participants documented the shade of those tabs using another set of shade guide using the right eye (left eye covered), left eye (right eye covered), as well as both eyes. Test for ocular dominance was performed using the Dolman method. The results were statistically analyzed using the chi-square test with a level of significance set at < .05. The percentage of correct shade matching with the monocular dominant vision (53%) was significantly better as compared to the monocular non-dominant vision (12%) (P < .001) or binocular vision (44%) (P < .05). Sex had an influence in shade selection (P = .031). However, clinical experience was an insignificant aspect in shade matching (P = .078). Knowing the clinician's dominant eye can be clinically relevant, as it can influence the accuracy of shade selection, irrespective of sex and clinical experience.


Accelerating ptychographic reconstructions using spectral initializations.
Ptychography is a promising phase retrieval technique for label-free quantitative phase imaging. Recent advances in phase retrieval algorithms witnessed the development of spectral methods to accelerate gradient descent algorithms. Using spectral initializations on experimental data, for the first time, we report three times faster ptychographic reconstructions than with a standard gradient descent algorithm and improved resilience to noise. Coming at no additional computational cost compared to gradient-descent-based algorithms, spectral methods have the potential to be implemented in large-scale iterative ptychographic algorithms.


Sleep-wake behavior in the rat: ultradian rhythms in a light-dark cycle and continuous bright light.
Ultradian rhythms are a prominent but little-studied feature of mammalian sleep-wake and rest-activity patterns. They are especially evident in long-term records of behavioral state in polyphasic animals such as rodents. However, few attempts have been made to incorporate ultradian rhythmicity into models of sleep-wake dynamics, and little is known about the physiological mechanisms that give rise to ultradian rhythms in sleep-wake state. This study investigated ultradian dynamics in sleep and wakefulness in rats entrained to a 12-h:12-h light-dark cycle (LD) and in rats whose circadian rhythms were suppressed and free-running following long-term exposure to uninterrupted bright light (LL). We recorded sleep-wake state continuously for 7 to 12 consecutive days and used time-series analysis to quantify the dynamics of net cumulative time in each state (wakefulness [WAKE], rapid eye movement sleep [REM], and non-REM sleep [NREM]) in each animal individually. Form estimates and autocorrelation confirmed the presence of significant ultradian and circadian rhythms; maximum entropy spectral analysis allowed high-resolution evaluation of multiple periods within the signal, and wave-by-wave analysis enabled a statistical evaluation of the instantaneous period, peak-trough range, and phase of each ultradian wave in the time series. Significant ultradian periodicities were present in all 3 states in all animals. In LD, ultradian range was approximately 28% of circadian range. In LL, ultradian range was slightly reduced relative to LD, and circadian range was strongly attenuated. Ultradian rhythms were found to be quasiperiodic in both LD and LL. That is, ultradian period varied randomly around a mean of approximately 4 h, with no relationship between ultradian period and time of day.


Comparative Analysis of Spray-Dried Porcine Plasma and Hydrolyzed Porcine Protein as Animal-Blood-Derived Protein Ingredients for Pet Nutrition.
Spray-dried porcine plasma (SDPP) and hydrolyzed porcine protein (HPP) are promising animal protein ingredients sourced from healthy animal blood that are rich in biomolecules, including immunoglobulins, and can be an appropriate and valuable animal protein ingredient to supply the growing need for ingredients that meet the natural needs of carnivorous pets. The aim of this preliminary study was to analyze the chemical composition and mineral profile of a novel HPP compared with results for SDPP. The basic composition analysis followed AOAC guidelines, and the elemental analysis utilized atomic absorption spectrometry. Statistical comparisons employed an independent Student's t-test (p < 0.05). Both SDPP and HPP are low in moisture (<4.3%) and rich in protein, with SDPP significantly exceeding HPP (75.4% vs. 71.4%). They boast mineral richness indicated by crude ash content (12.7% and 12.5%), featuring Na, K, P, and the trace elements Mo, Fe, and Zn. Notably, SDPP contains elevated molybdenum levels (51.39 mg/100 g vs. 10.93 mg/100 g in HPP), an essential element for diverse animal functions. Quantifying these elements in raw materials aids in achieving optimal nutrient levels in the final product. The study underscores SDPP as an excellent protein source, confirming that its nutritional value is similar to or better than other protein components in pet food.


Aberrant GRK6 promoter methylation is associated with poor prognosis in hypopharyngeal squamous cell carcinoma.
Hypopharyngeal squamous cell carcinoma (HSCC) is one of the most common head and neck cancers with high invasiveness and poor prognosis. To identify targeted therapeutics against metastasis, a better understanding of the regulation of HSCC cell invasion is needed. In recent years, G protein-coupled receptor kinases (GRKs) have been implicated in cancer metastasis through phosphorylation of the activated form of G protein coupled receptors (GPCRs). However, there is little information regarding GRKs expression in HSCC. In the present study, we examined GRK6 expression in HSCC and also assessed the possible cause of its aberrant expression, as well as its clinical significance. Real-time quantitative PCR (qPCR) and western blotting were performed to analyze the expression of GRK6 in HSCC tissues and corresponding non-malignant tissues. Subsequently, paired HSCC and corresponding non-malignant tissues were evaluated for the methylation status of GRK6 gene promoter using methylation-specific PCR (MSP). Furthermore, we investigated the methylation status and the clinicopathological significance of GRK6 in 45 paired HSCC and corresponding non-malignant tissues. The suppression of GRK6 in hypopharyngeal cell line FaDu by GRK6-shRNA lentivirus transfection was utilized to detect the role of GRK6 in hypopharyngeal cancer progression. Our results showed that the expression of GRK6 mRNA and protein was significantly lower in HSCC than in corresponding adjacent non-tumor tissues, and this downregulation was found to be in accordance with aberrant methylation of the gene. Hypermethylation of the gene was observed in 77.8% (35/45) of the HSCC tissues, while it was found in only 42.2% (19/45) of the corresponding non-malignant tissues. GRK6 methylation was related to depth of tumor invasion and TNM stage. Upon treatment with 5-aza-2'-deoxycytidine, GRK6 expression was upregulated in FaDu cells, and cell invasion was signinficantly inhibited. Furthermore, the suppression of GRK6 by shRNA transfection enhanced FaDu cells invasion. Our results indicate that the aberrant methylation of GRK6 gene promoter may underlie its downregulation in HSCC, and may play an important role in the metastasis of HSCC.


How We Become Who We Are: Ashley, Carla, and the Rest of Us.
Lisa Freitag and Joan Liaschenko's thoughtful and important article goes directly to the under-examined heart of Ashley's case, namely to what sustains her in a habitable and intelligible identity. Though quite sympathetic with their conclusion and line of argument, I try to trouble their proceedings a bit, largely by wondering how having a specific such identity, out of several that may be in-principle available, matters to someone with Ashley's cognitive scope. I do this not simply to be contrary, but because their article also seems to me to raise issues in the ethics of bioethics-in particular, what I call the dilemma of ethical endeavor: How ought one publicly pursue deeply important and complex issues, the very raising of which may offend interlocutors who indeed have grounds for resentment. Making a habit of second guessing oneself may be part of the answer.


A new class of modular P,N-ligand library for asymmetric Pd-catalyzed allylic substitution reactions: a study of the key Pd-pi-allyl intermediates.
A new class of modular P,N-ligand library has been synthesized and screened in the Pd-catalyzed allylic substitution reactions of several substrate types. These series of ligands can be prepared efficiently from easily accessible hydroxyl-oxazole/thiazole derivatives. Their modular nature enables the bridge length, the substituents at the heterocyclic ring and in the alkyl backbone chain, the configuration of the ligand backbone, and the substituents/configurations in the biaryl phosphite moiety to be easily and systematically varied. By carefully selecting the ligand components, therefore, high regio- and enantioselectivities (ee values up to 96 %) and good activities are achieved in a broad range of mono-, di-, and trisubstituted linear hindered and unhindered substrates and cyclic substrates. The NMR spectroscopic and DFT studies on the Pd-pi-allyl intermediates provide a deeper understanding of the effect of ligand parameters on the origin of enantioselectivity.


[Induction of SOS-response of cells exposed to autoregulatory factors of microorganisms].
Among examined microbial growth regulators of alkyl hydroxybenzene group (hexylresorcinol, methylresorcinol, and hydroxyethylphenol), only hexylresorcinol induces cellular SOS response, demonstrating a dose-dependent increase of the induction factor in the SOS chromotest with the Escherichia coli PQ37 strain. At the highest of used concentrations (100 micrograms/ml), hydroxyethylphenol and nonalkylated resorcinol were shown to exert a weak toxic effect, reducing the activity of constitutive alkaline phosphatase, but did not induce SOS response. Nontoxic methylresorcinol did not induce genome damage, which can trigger SOS functions. It is concluded that substitutions in phenolic ring affect genotoxic activity of alkylresorcinols.


Comparison of microbial populations in the small intestine, large intestine and feces of healthy horses using terminal restriction fragment length polymorphism.
The composition of the microbiota of the equine intestinal tract is complex. Determining whether the microbial composition of fecal samples is representative of proximal compartments of the digestive tract could greatly simplify future studies. The objectives of this study were to compare the microbial populations of the duodenum, ileum, cecum, colon and rectum (feces) within and between healthy horses, and to determine whether rectal (fecal) samples are representative of proximal segments of the gastrointestinal tract. Intestinal samples were collected from ten euthanized horses. 16S rRNA gene PCR-based TRFLP was used to investigate microbiota richness in various segments of the gastrointestinal tract, and dice similarity indices were calculated to compare the samples. Within horses large variations of microbial populations along the gastrointestinal tract were seen. The microbiota in rectal samples was only partially representative of other intestinal compartments. The highest similarity was obtained when feces were compared to the cecum. Large compartmental variations were also seen when microbial populations were compared between six horses with similar dietary and housing management. Rectal samples were not entirely representative of intestinal compartments in the small or large intestine. This should be taken into account when designing studies using fecal sampling to assess other intestinal compartments. Similarity between horses with similar dietary and husbandry management was also limited, suggesting that parts of the intestinal microbiota were unique to each animal in this study.


Automatic hoof-on and -off detection in horses using hoof-mounted inertial measurement unit sensors.
For gait classification, hoof-on and hoof-off events are fundamental locomotion characteristics of interest. These events can be measured with inertial measurement units (IMUs) which measure the acceleration and angular velocity in three directions. The aim of this study was to present two algorithms for automatic detection of hoof-events from the acceleration and angular velocity signals measured by hoof-mounted IMUs in walk and trot on a hard surface. Seven Warmblood horses were equipped with two wireless IMUs, which were attached to the lateral wall of the right front (RF) and hind (RH) hooves. Horses were walked and trotted on a lead over a force plate for internal validation. The agreement between the algorithms for the acceleration and angular velocity signals with the force plate was evaluated by Bland Altman analysis and linear mixed model analysis. These analyses were performed for both hoof-on and hoof-off detection and for both algorithms separately. For the hoof-on detection, the angular velocity algorithm was the most accurate with an accuracy between 2.39 and 12.22 ms and a precision of around 13.80 ms, depending on gait and hoof. For hoof-off detection, the acceleration algorithm was the most accurate with an accuracy of 3.20 ms and precision of 6.39 ms, independent of gait and hoof. These algorithms look highly promising for gait classification purposes although the applicability of these algorithms should be investigated under different circumstances, such as different surfaces and different hoof trimming conditions.


Biosynthesis and release of platelet-activating factor from human monocytes.
The aim of the present study was to investigate the pathways of platelet-activating factor (PAF) production and release from human monocytes. For this purpose, both phagocytic stimuli and stimuli induced by soluble agents were used. The phagocytic stimuli exerted their effect in a receptor-specific mechanism related to surface Fc, C3b and C3d receptors. Stimuli induced by soluble agents, such as A23187 and pH 10.6, which do not require interaction with specific receptors, were also effective in inducing PAF release. In contrast, C5a, a soluble agent which induces a receptor-mediated release of PAF from neutrophils, failed to induce PAF release from monocytes. PAF release from monocytes could be dissociated from phagocytosis and from release of lysozyme. The PAF release required the presence of extracellular cations, the activation of membrane esterase and phospholipase A2 and the integrity of the microfilament system. Moreover, PAF release was modulated by lipoxygenase and intracellular cAMP levels. The relevance of an acetylation process in the biosynthesis of PAF was suggested by the increase of PAF yields in the presence of sodium acetate and by the incorporation of 14C-sodium acetate into molecules of active PAF.


CaMADS1, a MADS box gene expressed in the carpel of hazelnut.
Hazelnut (Corylus avellana L.) is a species of economic interest that shows a peculiar floral biology. Unlike most of the angiosperms, which produce ovules during floral development such that they are ready for pollen at anthesis, hazelnut ovary development is delayed and triggered by compatible pollination. In order to elucidate the mechanisms regulating this unusual process and the role of the MADS box genes in ovary development, a cDNA library from pollinated styles of hazelnut was screened with a mixture of MADS box genes from different plant species. CaMADS1 (Corylus avellana MADS box), a floral-specific MADS box gene, was isolated, and characterized as belonging to the sub-family of the AGAMOUS genes. Northern blot, RT-PCR analyses and in situ hybridization experiments show a precise correlation between ovary development and CaMADS1 expression, indicating a role of this MADS box gene in the processes of floral organogenesis.


Fine architecture of the fascial planes around the lateral femoral cutaneous nerve at its pelvic exit: an epoxy sheet plastination and confocal microscopy study.
Meralgia paresthetica is commonly caused by mechanical entrapment of the lateral femoral cutaneous nerve (LFCN). The entrapment often occurs at the site where the nerve exits the pelvis. Its optimal surgical management remains to be established, partly because the fine architecture of the fascial planes around the LFCN has not been elucidated. The aim of this study was to define the fascial configuration around the LFCN at its pelvic exit. Thirty-six cadavers (18 female, 18 male; age range 38-97 years) were used for dissection (57 sides of 30 cadavers) and sheet plastination and confocal microscopy (2 transverse and 4 sagittal sets of slices from 6 cadavers). Thirty-four healthy volunteers (19 female, 15 male; age range 20-62 years) were examined with ultrasonography. The LFCN exited the pelvis via a tendinous canal within the internal oblique-iliac fascia septum and then ran in an adipose compartment between the sartorius and iliolata ligaments inferior to the anterior superior iliac spine (ASIS). The iliolata ligaments newly defined and termed in this study were 2-3 curtain strip-like structures which attached to the ASIS superiorly, were interwoven with the fascia lata inferomedially, and continued laterally as skin ligaments anchoring to the skin. Between the sartorius and tensor fasciae latae, the LFCN ran in a longitudinal ligamental canal bordered by the iliolata ligaments. This study demonstrated that 1) the pelvic exit of the LFCN is within the internal oblique aponeurosis and 2) the iliolata ligaments form the part of the fascia lata over the LFCN and upper sartorius. These results indicate that the internal oblique-iliac fascia septum and iliolata ligaments may make the LFCN susceptible to mechanical entrapment near the ASIS. To surgically decompress the LFCN, it may be necessary to incise the oblique aponeurosis and iliac fascia medial to the LFCN tendinous canal and to free the iliolata ligaments from the ASIS.


Studies on the effects of histamine on cholinergic transmission to the heart and vasculature in the anesthetized cat.
Intravenous infusion of histamine, 2 to 16 micro g/kg/min, failed to alter bradycardic responses to electrical stimulation of the vagus in anesthetized cats. In this respect, effect of this substance differed from those observed in anesthetized dogs. However, infusion of histamine, 2 micro g/kg/min, significantly attenuated vasodilator responses induced by electrical stimulation of the lumbar sympathetic chain in bretylium pretreated cats. This action of histamine on the cholinergic vasodilator system could be completely antagonized by the simultaneous administration of pyrilamine and metiamide. Histamine also inhibited vascular effects of acetylcholine and prostaglandin E1(PGE1). Thus it appears that the ability of histamine to attenuate cholinergic vasodilatation is due to a nonspecific antagonism of the neurohumor at the level of blood vessels. Since histamine has been shown also to inhibit sympathetic transmission by a presynaptic mechanism, it is suggested that histamine could influence vascular effects of both components of the autonomic nervous system.


Is there a geographical pattern in the breeding system of a complex of hermaphroditic slugs (Mollusca: Gastropoda: Carinarion)?
Allozyme analyses of the hermaphroditic slugs Arion (Carinarion) fasciatus, A. (C.) circumscriptus and A. (C.) silvaticus have suggested that the three species in North America and north-west Europe predominantly reproduce uniparentally, most probably by selfing. We used allozyme electrophoresis to investigate the population genetic structure of these species throughout a larger part of their native European distribution. Our results show that the previously reported "species" specific allozyme markers are no longer valid if populations from central Europe are investigated, and A. fasciatus and A. silvaticus appear to be "paraphyletic" taxa. In contrast to the general belief that selfing organisms show low gene diversities, the high selfing rates in N-NE European Carinarion do not necessarily result in low gene diversities. Moreover, our data suggest a geographical pattern in the prevalence of outcrossing, at least in A. fasciatus, with selfing in N-NE Europe and a mixed breeding system (i.e. selfing and outcrossing) in central Europe. Possible scenarios for the disjunct distribution of breeding systems in Carinarion are discussed.


Contracture and catecholamines in mammalian myocardium.
Contractures induced by KCl are produced in cat ventricular muscle after depletion of catecholamine stores by previous treatment with reserpine or by selective blocking of adrenergic receptor sites with propranalol. Contractures are reproducible for 2 to 3 hours and are markedly depressed by the addition of epinephrine. The relaxation of contracture induced by epinephrine parallels the eftect of this compound of shortening the duration of the normal twitch. The failure of the normal mammalian myocardium to maintain tension in solutions of high KCI concentration appears to be related to the endogenous amounts of catecholamines in the tissue.


The role of growth hormone in diabetes mellitus.
The insulin and growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis are two endocrine systems that are interlinked at many levels. GH is one of the glucose counter-regulatory hormones, rising in response to hypoglycaemia, it has both intrinsic hyperglycaemic actions and causes insulin resistance. Both IGF-I and its receptor have high structural and functional homology to insulin and its receptor. Insulin can regulate IGF-I production, acting on the GH receptor or at a post-receptor site. Conversely IGF-I is thought to have a permissive effect on the pancreatic insulin response to glucose. Growth is compromised in poorly controlled diabetic children; however, a causal link with altered GH/IGF-I levels has not been proven. Insulin-dependent diabetes clearly causes derangements in the GH/IGF-I axis. In poorly controlled diabetics GH levels are invariably raised whilst normal or low levels of IGF-I are found, indicating a dissociation between the two factors. Altered IGF-binding protein levels are also found, with high levels of small binding protein and low levels of large binding protein. These derangements are probably the result of interactions at many levels although the exact mechanisms are not fully understood. Raised GH levels could result from altered hypothalamic/pituitary control or reduced feedback inhibition. The latter could, in turn, result from low IGF-I levels, reduced availability of IGF-I to relevant receptors or increased levels of inhibitors (possibly the small binding protein). Low IGF-I levels could be directly due to deficient insulin levels or simply to lack of available circulating binding protein. Alternative or altered molecular forms of circulating GH in diabetes seem unlikely on present evidence. That GH has an effect on glycaemic control is most evident from the abnormal glucose tolerance seen in acromegalics, but is also seen with physiological GH variations such as during the pubertal growth spurt. In diabetics the derangements to the GH/IGF-I axis, caused by poor metabolic control, leads to aggravation of the metabolic problems. Altered GH/IGF-I levels have been implicated in the long-term complications associated with diabetes, and whilst GH/IGF-I are not essential for the early changes involved in these complications they may still play an important role in their development, especially proliferative retinopathy.


Enteral nutrition delivery technique.
Ingestion and absorption of a nutritionally adequate diet is necessary to maintain normal body composition and organ function. Patients with all kinds of diseases are at increased risk of developing nutritional abnormalities from anorexia, dietary restriction, malabsorption, increased intestinal losses or altered nutrient requirements. Therefore, it is important for doctors to understand the general principles of clinical nutrition for optimal management of patients with various disorders. The purpose of this review is to highlight an important aspect of nutrition: methods for enteral nutrient delivery. Enteral feeding is the preferred method to provide nutritional support in patients who cannot or will not eat but who have a functional gastrointestinal tract. The placement of a small-diameter nasogastric or nasoduodenal tube is the simplest technique for feeding patients who are unlikely to require tube feeding for more than 6 weeks. Gastrostomy, gastrojejunostomy and jejunostomy tubes placed by using endoscopic, radiologic, or surgical techniques should be considered in patients who require long-term feeding. With newer endoscopic feeding techniques replacing more conventional surgical techniques, this review proposes to discuss the newer developments in techniques of enteral feeding. This review will briefly discuss the principles governing nasoenteral feeding and will describe in detail the endoscopic assisted methods for placing enteral feeding tubes. These include percutaneous endoscopic gastrostomy, jejunal extension through a percutaneous endoscopic gastrostomy or direct endoscopic jejunostomy. It will also discuss the procedural complications and long term results of these methods of enteral feeding. Lastly the latest innovation in enteral feed - the one step button - is also discussed. Percutaneous endoscopic gastrostomy placement is an appropriate method for providing nutrition in ill patients if no contraindication to enteral feeding exists. In certain situations, percutaneous endoscopic gastrostomy placement may even be used to make the life of a terminally ill patient comfortable.


Environmental DNA (eDNA) metabarcoding assays to detect invasive invertebrate species in the Great Lakes.
Describing and monitoring biodiversity comprise integral parts of ecosystem management. Recent research coupling metabarcoding and environmental DNA (eDNA) demonstrate that these methods can serve as important tools for surveying biodiversity, while significantly decreasing the time, expense and resources spent on traditional survey methods. The literature emphasizes the importance of genetic marker development, as the markers dictate the applicability, sensitivity and resolution ability of an eDNA assay. The present study developed two metabarcoding eDNA assays using the mtDNA 16S RNA gene with Illumina MiSeq platform to detect invertebrate fauna in the Laurentian Great Lakes and surrounding waterways, with a focus for use on invasive bivalve and gastropod species monitoring. We employed careful primer design and in vitro testing with mock communities to assess ability of the markers to amplify and sequence targeted species DNA, while retaining rank abundance information. In our mock communities, read abundances reflected the initial input abundance, with regressions having significant slopes (p<0.05) and high coefficients of determination (R2) for all comparisons. Tests on field environmental samples revealed similar ability of our markers to measure relative abundance. Due to the limited reference sequence data available for these invertebrate species, care must be taken when analyzing results and identifying sequence reads to species level. These markers extend eDNA metabarcoding research for molluscs and appear relevant to other invertebrate taxa, such as rotifers and bryozoans. Furthermore, the sphaeriid mussel assay is group-specific, exclusively amplifying bivalves in the Sphaeridae family and providing species-level identification. Our assays provide useful tools for managers and conservation scientists, facilitating early detection of invasive species as well as improving resolution of mollusc diversity.


Perivascular neuritic dystrophy associated with cerebral amyloid angiopathy in Alzheimer's disease.
Cerebral amyloid angiopathy (CAA) affects both leptomeningeal and parenchymal blood vessels and is common in Alzheimer's disease (AD). In some vessels, CAA is accompanied by localized neuritic dystrophy around the affected blood vessel. The aim of this study was to assess the distribution and severity of perivascular neuritic dystrophy in primary visual and visual association cortices. The severity of perivascular neuritic dystrophy and Abeta deposition was scored in an association cortex (Brodmann area 18) and a primary cortex (Brodmann area 17) with double labeling immunohistochemistry for tau and Abeta in 31 cases of AD with severe CAA. The perivascular tau neuritic dystrophy score was significantly worse in visual association cortex than in primary visual cortex. On the other hand, there was no difference in the perivascular Abeta score between the two cortices. There were positive correlations between the severity of perivascular tau and perivascular Abeta scores for both primary and association cortices. The results suggest that the local neuronal environment determines the severity and nature of the perivascular neuritic pathology more than the severity of the intrinsic vascular disease and suggest a close association between perivascular amyloid deposits, so-called dyshoric angiopathy, and perivascular neuritic dystrophy.


Physician's knowledge and treatment of primary dysmenorrhea.
Recent advances in knowledge have increased understanding of the etiology of primary dysmenorrhea and provided new approaches to the treatment of this disorder. Primary care physicians in Missouri have been surveyed to determine the extent to which new knowledge about primary dysmenorrhea has been utilized in patient care. The majority of physicians who responded to a mailed questionnaire were aware of the role of prostaglandins in the pathogenesis of dysmenorrhea and used prostaglandin inhibitors in management. Congenital cervical stenosis, neurosis, and physical inactivity were also frequently cited as causal factors of this disorder. Older physicians and osteopathic physicians were less likely to prescribe prostaglandin synthetase inhibitors for this condition. The reported prevalence of dysmenorrhea in the respondent's practice was lower than that estimated in the literature. The findings suggest that the condition is underdiagnosed and that effective pharmacotherapy may be underutilized.


Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown.
The cannabinoid CB1 and CB2 receptors are Class A G protein-coupled receptors (GPCRs). While many Class A GPCRs have endogenous ligands that are hydrophilic cations (e.g., the serotonin and dopamine receptors), the cannabinoid receptors have neutral, highly lipophilic ligands derived from the fatty acid, arachidonic acid. The most well-studied of these are N-arachidonoylethanolamine (anandamide, AEA) and sn-2-arachidonoylglycerol (2-AG). This review focuses on the experimental and computational studies that have been used to probe the nature of endocannabinoid interaction with the cannabinoid receptors. These studies include mutation, SAR and NMR studies, as well as, QSAR, docking and molecular dynamics simulations. Gaps in our knowledge are identified. The review begins more generally, however, by discussing the entire endocannabinoid system, of which the cannabinoid receptors are part. For in order to understand endocannabinoid action, one needs an appreciation for the environments for which these ligands have been designed and the conformational changes these ligands must undergo in order to act on the cannabinoid receptors.


Output feedback fuzzy controller design with local nonlinear feedback laws for discrete-time nonlinear systems.
This paper considers the output feedback control problem for nonlinear discrete-time systems, which are represented by a type of fuzzy systems with local nonlinear models. By using the estimations of the states and nonlinear functions in local models, sufficient conditions for designing observer-based controllers are given for discrete-time nonlinear systems. First, a separation property, i.e., the controller and the observer can be independently designed, is proved for the class of fuzzy systems. Second, a two-step procedure with cone complementarity linearization algorithms is also developed for solving the H( ∞) dynamic output feedback (DOF) control problem. Moreover, for the case where the nonlinear functions in local submodels are measurable, a convex condition for designing H(∞) controllers is given by a new DOF control scheme. In contrast to the existing methods, the new methods can design output feedback controllers with fewer fuzzy rules as well as less computational burden, which is helpful for controller designs and implementations. Lastly, numerical examples are given to illustrate the effectiveness of the proposed methods.


Differential effects of emotional cues on components of prospective memory: an ERP study.
So far, little is known about the neurocognitive mechanisms associated with emotion effects on prospective memory (PM) performance. Thus, this study aimed at disentangling possible mechanisms for the effects of emotional valence of PM cues on the distinct phases composing PM by investigating event-related potentials (ERPs). Participants were engaged in an ongoing N-back task while being required to perform a PM task. The emotional valence of both the ongoing pictures and the PM cues was manipulated (pleasant, neutral, unpleasant). ERPs were recorded during the PM phases, such as encoding, maintenance, and retrieval of the intention. A recognition task including PM cues and ongoing stimuli was also performed at the end of the sessions. ERP results suggest that emotional PM cues not only trigger an automatic, bottom-up, capture of attention, but also boost a greater allocation of top-down processes. These processes seem to be recruited to hold attention toward the emotional stimuli and to retrieve the intention from memory, likely because of the motivational significance of the emotional stimuli. Moreover, pleasant PM cues seemed to modulate especially the prospective component, as revealed by changes in the amplitude of the ERP correlates of strategic monitoring as a function of the relevance of the valence for the PM task. Unpleasant pictures seemed to modulate especially the retrospective component, as revealed by the largest old/new effect being elicited by unpleasant PM pictures in the recognition task.


Studies on Chrysomyia albiceps (Wiedemann) one of the most important carrion flies in Egypt.
Chrysomyia albiceps often feeds to repletion and then regurgitates a portion of the food, a behaviour that heightens its importance as a mechanical vector of enteric pathogens. Pupae of this fly are susceptible to the attack of the parasitic wasp, Nasonia vitripennis in the laboratory as well as in nature at different underground depths where they pupate. The fly needs to feed on proteinaceous meals to start and complete its ovarian development. Liver, beef, camel, chicken, rabbit and fish meat were tested. Of the 6 tested diets, liver proved to be the most advantageous as 98% pupation was obtained, while with beef, camel, chicken, rabbit and fish 95.2%, 95.9%, 90.9%, 89.1% and 86% pupation, respectively, were obtained. Field observations revealed that Chrysomyia albiceps prefers to breed in big carcasses over small ones as the latter contain less moisture or amount of food and are subjected to desiccation and consumption before the full growth of larvae especially during the hot and dry months. Anatomical studies of the females attracted to a piece of meat in laboratory and outdoors experiments showed that the degree of ovarian development is variable including completely undeveloped ovaries, sexually mature ones and different stages of ovarian development. So, attraction to meat fulfill to important functions: nutrition and oviposition. Feeding visits are short in duration (6.2 +/- 2.1 min) and behaviourally simple. The oviposition visits last from 40-60 min with more complex behaviour which can be divided into the time before, during and after oviposition. Females in selecting a place for oviposition, preferred the softer places of the fresh meat; round its lower moist edge where much liquid food is present and where the females oviposit in groups at one location. When a female began to oviposit, it was joined by others that located the eggs with their ovipositors and started to oviposit where a clumped irregular egg masses are deposited.


Influences of agents with a self-reputation awareness component in an evolutionary spatial IPD game.
Iterated prisoner's dilemma (IPD) researchers have shown that strong positive reputations plus an efficient reputation evaluation system encourages both sides to pursue long-term collaboration and to avoid falling into mutual defection cycles. In agent-based environments with reliable reputation rating systems, agents interested in maximizing their private interests must show concern for other agents as well as their own self-reputations--an important capability that standard IPD game agents lack. Here we present a novel learning agent model possessing self-reputation awareness. Agents in our proposed model are capable of evaluating self-behaviors based on a mix of public and private interest considerations, and of testing various solutions aimed at meeting social standards. Simulation results indicate multiple outcomes from the addition of a small percentage of self-reputation awareness agents: faster cooperation, faster movement toward stability in an agent society, a higher level of public interest in the agent society, the resolution of common conflicts between public and private interests, and a lower potential for rational individual behavior to transform into irrational group behavior.


Biochemistry: a cadmium enzyme from a marine diatom.
The ocean biota contains a vast reservoir of genomic diversity. Here we present the sequence and preliminary characterization of a protein that is a cadmium-containing carbonic anhydrase from the marine diatom Thalassiosira weissflogii. The existence of a cadmium enzyme in marine phytoplankton may indicate that there is a unique selection pressure for metalloenzymes in the marine environment, and our discovery provides a long-awaited explanation for the nutrient-like behaviour of cadmium in the oceans.


The effects of sustained incisal clenching on the temporomandibular joint space.
To determine the effect of sustained incisal clenching on the width of the temporomandibular joint space. Nine normal subjects clenched on an anterior appliance for 10 min at 49 N. Sagittal tomograms were obtained during comfortable closure in the intercuspal position (ICP) (ICP-Before), comfortable closure on bite force transducer without clenching (BFT-Before), start of clenching (BFT-0), end of 5 min clenching (BFT-5), end of 10 min clenching (BFT-10), comfortable closure on the bite force transducer immediately after clenching (BFT-After) and comfortable closure in ICP after clenching (ICP-After). Joint space dimensions were automatically measured by a computerized image analysis system. The minimum joint space dimension was significantly reduced at BFT-5 (P = 0.0381), BFT-10 (P = 0.0019) and BFT-After (P = 0.0053) in relation to BFT-Before. The condylar position was also significantly shifted upward at BFT-0 (P = 0.0422), BFT-5 (P = 0.0005), BFT-10 (P = 0.0001), and BFT-After (P = 0.0004) in relation to BFT-Before. Sustained incisal clenching at 49 N causes significant anterior joint space reduction. We believe this is due to marked compression of the articular cartilage and disc.


Genome-Wide Changes of Regulatory Non-Coding RNAs Reveal Pollen Development Initiated at Ecodormancy in Peach.
Bud dormancy is under the regulation of complex mechanisms including genetic and epigenetic factors. To study the function of regulatory non-coding RNAs in winter dormancy release, we analyzed the small RNA and long non-coding RNA (lncRNA) expression from peach (Prunus persica) floral buds in endodormancy, ecodormancy and bud break stages. Small RNAs underwent a major shift in expression primarily between dormancy and flowering with specific pairs of microRNAs and their mRNA target genes undergoing coordinated differential expression. From endodormancy to ecodormancy, ppe-miR6285 was significantly upregulated while its target gene, an ASPARAGINE-RICH PROTEIN involved in the regulation of abscisic acid signaling, was downregulated. At ecodormancy, ppe-miR2275, a homolog of meiosis-specific miR2275 across angiosperms, was significantly upregulated, supporting microsporogenesis in anthers at a late stage of dormancy. The expression of 785 lncRNAs, unlike the overall expression pattern in the small RNAs, demonstrated distinctive expression signatures across all dormancy and flowering stages. We predicted that a subset of lncRNAs were targets of microRNAs and found 18 lncRNA/microRNA target pairs with both differentially expressed across time points. The genome-wide differential expression and network analysis of non-coding RNAs and mRNAs from the same tissues provide new candidate loci for dormancy regulation and suggest complex noncoding RNA interactions control transcriptional regulation across these key developmental time points.


A mathematical model of the immune and neuroendocrine systems mutual regulation under the technogenic chemical factors impact.
The concept of the triad regulatory metasystem, which includes the neuroendocrine and immune regulation systems, is currently generally accepted. Changes occurring in each of the regulatory systems in response to the impact of technogenic chemical factors are also well known. This paper presents mathematical models of the immune and neuroendocrine system functioning, using the interaction between these systems in response to bacterial invasion as an example, and changes in their performance under exposure to chemical factors, taking into account the stage of functional disorders in a producing organ, using the performance of the bone marrow as an example.