Invertebrate and vertebrate predation rates in a hyperarid ecosystem following an oil spill.
Extreme temperatures and scarce precipitation in deserts have led to abiotic factors often being regarded as more important than biotic ones in shaping desert communities. The presumed low biological activity of deserts is also one reason why deserts are often overlooked by conservation programs. We provide the first quantification of predation intensity from a desert ecosystem using artificial sentinel prey emulating caterpillars, a standardized monitoring tool to quantify relative predation pressure by many invertebrate and vertebrate predators. The study was conducted in a protected natural area affected by oil spills in 1975 and 2014; hence, we assessed the potential effects of oil pollution on predation rates. We found that predation was mostly due to invertebrate rather than vertebrate predators, fluctuated throughout the year, was higher at the ground level than in the tree canopy, and was not negatively affected by the oil spills. The mean predation rate per day (12.9%) was within the range found in other ecosystems, suggesting that biotic interactions in deserts ought not to be neglected and that ecologists should adopt standardized tools to track ecological functions and allow for comparisons among ecosystems.


Effective doses in radiology and diagnostic nuclear medicine: a catalog.
Medical uses of radiation have grown very rapidly over the past decade, and, as of 2007, medical uses represent the largest source of exposure to the U.S. population. Most physicians have difficulty assessing the magnitude of exposure or potential risk. Effective dose provides an approximate indicator of potential detriment from ionizing radiation and should be used as one parameter in evaluating the appropriateness of examinations involving ionizing radiation. The purpose of this review is to provide a compilation of effective doses for radiologic and nuclear medicine procedures. Standard radiographic examinations have average effective doses that vary by over a factor of 1000 (0.01-10 mSv). Computed tomographic examinations tend to be in a more narrow range but have relatively high average effective doses (approximately 2-20 mSv), and average effective doses for interventional procedures usually range from 5-70 mSv. Average effective dose for most nuclear medicine procedures varies between 0.3 and 20 mSv. These doses can be compared with the average annual effective dose from background radiation of about 3 mSv.


Dye-ligand interactions with 1,25-dihydroxyvitamin D3-receptor complexes from chicken intestine.
A number of dye-ligand adsorbents have been examined for purifying and characterizing 1,25-dihydroxyvitamin D3-receptor complexes from intestines of vitamin D3-deficient chickens. In particular, several triazinyl dyes--Cibacron blue F3GA, Procion red HE3B, and Green A dye, immobilized to agarose via an ether linkage--retain specifically bound 1,25-dihydroxyvitamin D3-receptor complexes formed at 0-4 degrees which are eluted at high salt concentrations. Moreover, receptor binding to these dye-ligand matrices occurs in the presence and absence of sterol. At least for Cibacron blue, the strength of receptor binding depends critically on the method of dye coupling to matrix. The concentration of KCl required for elution of receptor from the triazine ether-linked matrix is greater than coupling through the amine of the anthraquinone via a 10-atom spacer arm approximately equal to coupling through the amine of the anthraquinone via an isourea bond greater than Cibacron blue dextran. Data are presented which demonstrate that sterol-receptor complexes formed at 25 degrees have reduced affinity for dye-ligands when compared with sterol-receptor complexes formed at 0-4 degrees. It is suggested that this finding is related to proteolytic alterations of the receptor, since limited digestion with trypsin can mimic this phenomenon and several protease inhibitors can reduce the thermal-induced alterations. Biospecific elution of receptor is demonstrated using synthetic polyribonucleotides. Preference for polyguanylic and polyinosinic acid is observed over several other polyribonucleotides and mononucleotides. The data in this study, viewed collectively, suggest that there is a specific interaction between the polynucleotide domain of the 1,25-dihydroxyvitamin D3-receptor and several triazinyl dye-ligands. It is concluded that these dye-ligands should prove to be of considerable interest for facile chromatography to purify and characterize this receptor.


[Adenocarcinomas of the urachus].
Tumors of the urachus account for 1% of all malignant bladder tumors and 20-39% of primary adenocarcinoma of the bladder. We report 4 cases (3 males, 1 female) of urachal adenocarcinoma. One of the patients had a signet ring cell tumor. The most common clinical sign was a suprapubic mass followed by hematuria. In three cases, cystoscopy revealed a mass at the level of the bladder dome. The IVP was normal in all but one patient in whom a filling defect at the level of the dome was evidenced by the cystogram. In one patient, CT revealed a fistulous track between the bladder and the tumor mass. Treatment was by surgery in all of the cases. Supratrigonal cystectomy and en bloc resection of the anterior infraumbilical abdominal wall was performed in 3 cases, followed by wide cystoplasty using intestine in 2 cases. One patient underwent radical cystectomy and Bricker urinary diversion. Two patients are alive and disease-free at 2 and 10 years, respectively. The other two patients have died; one following operation for high gastrointestinal hemorrhage, and the other at two years from generalized metastasis. The clinical findings reported in the literature, the diagnostic protocols and treatment of these tumor types are discussed.


Ligamentous anatomy of the distal clavicle.
We describe the insertional variations of supporting ligaments of the acromioclavicular joint, especially with respect to gender. We analyzed 41 cadaveric clavicles (22 female and 19 male) with attached ligaments. The distance between the insertion of the trapezoid ligament and the distal end of the clavicle was not significantly different between sexes, although that of the conoid ligament and the mean anteroposterior width of the distal clavicle was significantly greater in men. Although there are significant sex-related differences in the insertional distances of the CC ligaments, resection of less than 11.0 mm should not violate the trapezoid ligament and less than 24.0 mm should not violate the conoid ligament in either sex in 98% of the general population. Resection of more than 7.6 mm of the distal clavicle in men and 5.2 mm in women, performed by an arthroscopic approach, may violate the superior acromioclavicular ligament.


En bloc resections of bone tumors of the thoracolumbar spine. A preliminary report on 29 patients.
Twenty-nine patients with primary bone tumors and solitary metastases of the thoracolumbar spine treated with en bloc resection are reviewed retrospectively. To demonstrate the possibility to apply in the spine the same principles of surgical oncology adopted for primary bone tumors of the limbs. The surgical oncologic staging systems currently applied in limb tumor surgery are difficult to apply to spinal tumors. The anatomic conditions make extralesional surgery difficult or impossible, which has restrained a more common use of resection surgery in the spine. Focus is put on a new surgical staging system and en bloc vertebral resection. Twenty-five primary malignant and aggressive benign bone tumors and four solitary metastases were treated. The patients were submitted to oncologic and surgical staging for surgical planning. The primary tumors were classified according to Enneking system: three Stage IA, six Stage IB, eight Stage IIB, eight Stage 3 benign. Staging according to the Weinstein-Boriani-Biagini system was also done. Thirteen lesions involved the vertebral body; nine lesions developed in the posterior arch, or part of it, and seven lesions occupied part of the body and part of the arch. A careful anesthesiologic evaluation was performed as well as a continuous intraoperative on-line monitoring of the vital parameters. The en bloc resections (multisegmental in five patients) were performed in 10 thoracic, in 16 lumbar, in two thoracolumbar lesions, and in one lumbosacral lesion. Reconstruction was performed, aiming to replace the resected columns. The specimens were submitted to histologic study of the margins. All the patients were followed, and their status was defined on clinical and imaging studies. In 20 patients, a wide margin was achieved, in eight a marginal margin, in one an intralesional margin. The margin was contaminated in seven patients. Surgical time was 3-21 hours (average, 12 hours). No patient died during surgery or from surgical complications. Three mechanical failures of the implants required additional surgery. One deep infection arose. The only neurologic problems observed were related to the nerve roots sectioned for oncologic purpose. No local recurrence was found at follow-up evaluation after 6-134 months (average, 30 months). En bloc resection can be performed in selected tumors of the spine; the indication to such major surgery must be based on the oncologic stage, and the procedure must be carefully planned. For this purpose, the Weinstein-Boriani-Biagini system could be a helpful tool. Long-term results must be weighed before a definitive statement of the indications can be made.


Factors associated with age-disparate sexual partnerships among males and females in South Africa: a multinomial analysis of the 2012 national population-based household survey data.
In South Africa, age-disparate to sexual relationships where the age difference between partners is 5 years or greater is an important contributor to the spread of HIV. However, little is known about the predictors of age-disparate sexual relationships. This study investigates factors associated with age-disparate sexual relationships among males and females in South Africa. This analysis used the 2012 nationally representative population-based household survey conducted using multi-stage stratified cluster sampling design. Multivariate multinomial stepwise logistic regression models were used to determine factors associated with age-disparate sexual relationships. Of 15,717 participants, who responded to the question on age-disparate sexual relationships, 62% males versus 58.5% females had partners within 5 years older or younger, 34.7% of males versus 2.7% of females had partners at least 5 years younger and 3.3% of males versus 38.8% of females had partners at least 5 years older. Among both males and females predictors of age-disparate sexual relationships were education, employment, socioeconomic status, locality type, age at sexual debut, condom use at last sexual act and HIV status while race was also an additional predictor for among females. Including unprotected sex and risk of HIV infection among adolescent girls and young women with sexual partners 5 years older their age. This study suggest that there is a need for reprioritizing the combination of behavioural and structural interventions to address risky sexual behaviours, unprotected sex, poverty, limited education and gender inequitable norms related to age-disparate sexual relationships and HIV.


Improved viscosity modeling in patients with type 2 diabetes mellitus by accounting for enhanced red blood cell aggregation tendency.
Distorted wall shear stress (WSS) in patients with type 2 diabetes mellitus (T2DM) may be partly explained by an altered red blood cell aggregation tendency (RAT) on viscosity at low shear rate (SR). The present study evaluates viscosity modeling by implementation of hematocrit and RAT in patients with and without T2DM (non-T2DM). A Couette viscometer and LORCA aggregometer provided viscosity and RAT on 6 shear rates in 55 patients (46-78 yrs, 66% male, T2DM: n = 28), following informed consent. Using a K-fold cross-validation, two linear mixed models predicted by SR and Hct and by SR, Hct and RAT were compared. In non-T2DM modeling was improved in relatively low RATs (48%, p = 1.0 x 10-11) and became worse in relatively high RATs (-18%, p = 0.019). In T2DM the opposite was observed, as modeling became worse in relatively low RATs (-16%, p = 0.001) but was improved in relatively high RATs (22%, p = 0.022). In addition to confirming previous research, major differences in modeling improvement between T2DM and non-T2DM were found. Especially patients with T2DM, a high RAT and often high viscosity at low SR benefit from a more accurate viscosity modeling. Further studies should evaluate how these findings affect WSS in these patients.


Increased XRALDH2 activity has a posteriorizing effect on the central nervous system of Xenopus embryos.
Retinoic acid (RA) metabolizing enzymes play important roles in RA signaling during vertebrate embryogenesis. We have previously reported on a RA degrading enzyme, XCYP26, which appears to be critical for the anteroposterior patterning of the central nervous system (EMBO J. 17 (1998) 7361). Here, we report on the sequence, expression and function of its counterpart, XRALDH2, a RA generating enzyme in Xenopus. During gastrulation and neurulation, XRALDH2 and XCYP26 show non-overlapping, complementary expression domains. Upon misexpression, XRALDH2 is found to reduce the forebrain territory and to posteriorize the molecular identity of midbrain and individual hindbrain rhombomeres in Xenopus embryos. Furthermore, ectopic XRALDH2, in combination with its substrate, all-trans-retinal (ATR), can mimic the RA phenotype to result in microcephalic embryos. Taken together, our data support the notion that XRALDH2 plays an important role in RA homeostasis by the creation of a critical RA concentration gradient along the anteroposterior axis of early embryos, which is essential for proper patterning of the central nervous system in Xenopus.


Development of an avian brachial plexus nerve block technique for perioperative analgesia in mallard ducks (Anas platyrhynchos).
Surgical procedures of the wing are commonly performed in companion, captive, and wild avian species. To develop a clinically applicable brachial plexus nerve block technique for perioperative analgesia in birds, 8 adult female mallard ducks (Anas platyrhynchos) were anesthetized and used in several local anesthetic trials with bupivacaine (2 or 8 mg/kg) or a combination of lidocaine (15 mg/kg) and epinephrine (3.8 microg/kg) perineurally; equal volumes of saline were administered as control treatments. Both axillary and dorsal approaches to the brachial plexus were evaluated. With the axillary approach, radial and ulnar compound nerve action potentials (CNAP), sensory nerve conduction velocities (SNCVs), and cord dorsum potentials (CDPs) were recorded after distal sensory nerve stimulation. Values were recorded before and at 5, 30, and 60 minutes after injection of local anesthetic or saline. Birds were monitored for the presence of a wing droop and a change in motor function on recovery from anesthesia. Results were highly variable for all techniques. No technique significantly decreased CDPs or resulted in consistent wing droop. Radial and ulnar CNAPs, SNCVs, and CDPs were consistently recorded in all birds. Variable results might indicate that the treatment, concentration, or volume of local anesthetic used was ineffective in producing local anesthesia. Electrodiagnostic methods used in these ducks to assess loss of sensory nerve conduction might not be sensitive enough to assess the effects of local anesthesia. Further research is needed to identify methods for assessing the efficacy of brachial plexus nerve blockade in birds.


High Amounts of n-Alkanes in the Composition of Asphodelus aestivus Brot. Flower Essential Oil from Cyprus.
There is only a couple of reports indicating essential oil composition of Asphodelus species in the literature. However, from the members of this genus many non-volatile secondary metabolites were isolated. In Cyprus, Asphodelus aestivus Brot. can be found abundantly in all regions of the island. This plant has various ethnobotanical uses in Cyprus. There is no report on the volatiles nor the essential oil composition of A. aestivus. The smell of A. aestivus flowers resembles that of a cat pee which caught our attention. Therefore, we have carried out GC, GC/MS analysis of the essential oil (yield: 0.01 v/w) obtained from Asphodelus aestivus flowers. Seventeen compounds were identified in the essential oil comprising 96.2% of the oil. The major components of the essential oil were hexadecanoic acid 35.6%, pentacosane 17.4%, tricosane 13.4% and heptacosane 8.4%. In our results, we expected to see sulfur containing cat pee odorants due to the odor of the flower whereas high amounts of n-alkanes, saturated fatty acids and minor amounts of acyclic diterpenes were observed.


Electrophysiological and ultrastructural analysis of the neuromuscular blockade and miotoxicity induced by the Micrurus nigrocinctus snake venom.
Micrurus nigrocinctus is the most abundant coral snake in Central America. The venom of this specie induced a concentration-dependent (10-20 micrograms/ml) depolarization in the isolated mouse phrenic nerve-diaphragm preparations incubated at 37 degrees C. d-Tubocurarine (10 micrograms/ml) and (alpha beta ungarotoxin (3-5 micrograms/ml) were able to partially protect against the depolarization induced by the venom (10 micrograms/ml), suggesting the involvement of subsynaptic cholinergic receptors. This venom (10 micrograms/ml) also increased the frequency and amplitude of miniature end-plate potentials (mepps) during the first 10-20 min of incubation. Subsequently, the mepps progressively decreased and disappeared after 60 min. These responses were accompanied by ultrastructural changes involving the nerve terminals, the subsynaptic junctional folds and the muscle mitochondria. The synaptic gutter was shallow and, very often, "shrunken" terminals with omega-shaped axolemmal indentations and a decreased number of synaptic vesicles were present. A common finding was the presence of numerous finger-like, membrane-bounded bodies interposed between the terminal and the Schwann cells or postsynaptic sarcolemma. The preincubation of the venom with specific antivenom or the incubation of the preparations at room temperature (24-26 degrees C) reduced the number and intensity of the ultrastructural alterations. The last finding suggests the involvement of a enzymatic process, probably a phospholipase A2, present in the venom. There was a good correlation between the electrophysiological and ultrastructural effects induced by the venom which allow us to conclude that M. nigrocinctus venom has a presynaptic action in the initial stages of intoxication followed by sub- and postsynaptic effects, the last being the most important cause of neuromuscular blockade. A direct action of the venom on muscle fibers may also contributes to the irreversible blockade.


Pulmonary infection with influenza A virus induces site-specific germinal center and T follicular helper cell responses.
Protection from influenza A virus (IAV) challenge requires switched, high affinity Abs derived from long-lived memory B cells and plasma cells. These B cell subsets are generated in germinal centers (GCs), hallmark structures of T helper cell-driven B cell immunity. A full understanding of the GC reaction after respiratory IAV infection is lacking, as is the characterization of T follicular helper (T(FH)) cells that support GCs. Here, GC B cell and T(FH) cell responses were studied in mice following pulmonary challenge with IAV. Marked GC reactions were induced in draining lymph nodes (dLNs), lung, spleen and nasal-associated lymphoid tissue (NALT), although the magnitude and kinetics of the response was site-specific. Examination of switching within GCs demonstrated IgG2(+) cells to compose the largest fraction in dLNs, lung and spleen. IgA(+) GC B cells were infrequent in these sites, but composed a significant subset of the switched GC population in NALT. Further experiments demonstrated splenectomized mice to withstand a lethal recall challenge, suggesting the spleen to be unnecessary for long-term protection in spite of strong GC responses in this organ. Final studies showed that T(FH) cell numbers were highest in dLNs and spleen, and peaked in all sites prior to the height of the GC reaction. T(FH) cells purified from dLNs generated IL-21 and IFNγ upon activation, although CD4(+)CXCR5(-) T effector cells produced higher levels of all cytokines. Collectively, these findings reveal respiratory IAV infection to induce strong T helper cell-driven B cell responses in various organs, with each site displaying unique attributes.


[MR contrast media for cardiovascular imaging].
MR contrast media improve the diagnostic capability of MRI and MRA. They are used in the discrimination of viable and non-viable myocardium, transmural and non-transmural infarction, occlusive and reperfused infarction and for measurement of myocardial perfusion. Currently, clinical studies are almost completely restricted to the use of extracellular non-specific MR contrast media (i. e., Gd-DTPA, Gd-DTPA,-BMA, Gd-BOPTA, Gd-D03A). However, the feasibility of using intravascular, necrosis specific or intracellular MR contrast media or endogeneous substrates as specific MR contrast media in cardiovascular imaging has been demonstrated in experimental and a few clinical studies. Intravascular contrast media (i. e., MS-325 or NC100150 Injection) allow assessment of microvascular integrity and performance of MR angiography. Necrosis specific contrast media (i. e., Gadophrin-2) have been used for sizing the extent of infarcted myocardium while intracellular contrast media (i. e., Mn-DPDP) delineate viable myocardium. Endogenous contrast media (i. e., Deoxyhemoglobin, Na (+) or K (+)) have been tested for detecting the alterations in concentrations of these ions in infarcted myocardium and for perfusion measurements. Furthermore, intravascular MR contrast media may be useful for MRA and MRI guided cardiovascular interventions.


A New Species of Monocystis (Apicomplexa: Gregarina: Monocystidae) from the Asian Invasive Earthworm Amynthas agrestis (Megascolecidae), with an Improved Standard for Monocystis Species Descriptions.
Monocystis perplexa n. sp., a parasite of an important invasive Japanese earthworm in North America, Amynthas agrestis, is described from a site in Vermont. An improved standard for Monocystis species descriptions is proposed including a standard nomenclature to reduce synonymies, a standard set of biometrics and shape descriptions for living cells, and a DNA genomic sequence for the 18S rRNA (∼1,700 base pairs). Comparing morphologies of Monocystis parasites in sympatric earthworm species indicates that M. perplexa is specific to A. agrestis in the study region. Also, polymerase chain reaction primers specific to M. perplexa amplified samples of A. agrestis earthworms taken from several sites in Japan. This suggests the parasite entered North America from Japan, the origin of the invasive Amynthas earthworm, and thus M. perplexa would be the first Monocystis described from the diverse Japanese Amynthas earthworms and the first from East Asia. Monocystis perplexa was found in every population of A. agrestis surveyed in Vermont, always reaching 100% prevalence by late summer (the host has an annual life cycle in Vermont). The 18S gene sequence differed from that of Monocystis agilis from the sympatric earthworm Lumbricus terrestris (the only other sequence available for Monocystis), and a genetic similarity tree places them closest among other gregarines. Many of the 95 described species of Monocystis are very similar in morphology (based on species descriptions), so the 18S gene can act as a barcode for Monocystis species and thus will help to eliminate both synonymies and reveal cryptic species.


Effects of Low-Load, High-Repetition Resistance Training on Maximum Muscle Strength and Muscle Damage in Elite Weightlifters: A Preliminary Study.
This study aimed to assess the impact of different resistance training (RT) loads and repetition on muscle damage, intramuscular anabolic signaling, and maximal muscle strength (MMS) in weightlifters. Eighteen male weightlifters were randomly assigned to 8 weeks of supervised RT regimes: high-load, low-repetition (HL), low-load, high-repetition (LH), and combination of HL and LH (COMBI). All groups exhibited a significant increase in skeletal muscle mass (SMM) and growth hormone levels, which ultimately contributed to improvement in MMS as indicated by 1-repetition maximum in the back squat and back muscle strength. Notably, while there were no significant changes in the mTOR protein, the phosphorylation of phosphorylation of p70 ribosomal protein S6 kinase 1 (p70S6K1), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), and eukaryotic elongation factor 2 (eEF2), which are involved in muscle cell growth, was significantly affected by the different training regimens. More importantly, LH-RT led to a significant reduction in muscle damage markers, creatine kinase (CK) and lactate dehydrogenase (LDH), suggesting reduced recovery time and fatigue. Our results demonstrated that the LH-RT paradigm could be a viable alternative for weightlifters to enhance MMS and muscle hypertrophy similar to HL-RT, while reducing RT-induced muscle damage, ultimately contributing to the enhancement of exercise performance.


Tobacco and alcohol consumption among adolescents.
This study analyzes the consumption of alcohol and tobacco among high-school adolescents in the district of Porto, Portugal. The results reveal the following: the majority of respondents do not smoke; smoking starts earlier in the case of girls; smoking increases with age; peer pressure is an important factor influencing smoking; about half of adolescents consume alcohol; boys drink more than girls; the number of those who consume alcohol increases with age; distilled drinks are the choice for both genders; 44.1% of the respondents became intoxicated at least once and the majority has no intention to quit drinking.


Analysis of seroprevalence against Coxiella burnetii in a sample of farm workers in Western Sicily.
Little is known about the development of chronic Q fever caused by Coxiella burnetii in occupational risk groups and in the general population in Italy, as well as in many countries in the world. The aim of this study was to highlight the presence of the infection in a sample of workers operating outdoors (but not directly in contact with animals), in three provinces of western Sicily, in order to detect the human seroprevalence and compare the obtained data with those found in animals raised in the same territory. The study included 126 generic seasonal agricultural workers (labourers), 84 male and 42 female; none of whom were aware of any previous contact with Coxiella burnetii. Their immunologic status against Coxiella burnetii was tested through research and titration of both phases I and II specific antibodies (IgG) with an indirect immunofluorescence assay, using anti-antibodies labeled with fluorescein isothiocyanate. All data were statistically analyzed, comparing all positive results from the three provinces through variance analysis, and then comparing human results with those obtained from animals raised in the considered areas, specifically, 1,511 cows, 46 of which were found positive (3.04%), and 3,391 sheep, 548 of which were found positive (16.16%). Anti-Coxiella antibodies were found in nine of 42 females sampled (21.4%; 95%CI=[9.0-33.8]) and 21 of 84 males sampled (25.0%; 95%CI=[15.7-34.3]). 60% (18 of 30; 95%CI=[42.5-77.5]) of seropositive samples were positive either for Phase I antigen or for both Phase I and II antigens, representing cases of chronic infection. Applying Spearman's rank correlation, the percentage of seropositive humans was significantly correlated with that observed for sheep (r=1.00; p<0.001), but not for cows (r=-0.5; p=0.667). The results obtained, although based on a small sample, suggest that the disease is present in the territory of Western Sicily, both in animals and in humans. A closer collaboration between doctors and veterinarians is therefore necessary to fight against the spread of the infection.


Automated eligibility screening and monitoring for genotype-driven precision oncology trials.
The Information Systems Department at Memorial Sloan Kettering Cancer Center developed the DARWIN Cohort Management System (DCMS). The DCMS identifies and tracks cohorts of patients based on genotypic and clinical data. It assists researchers and treating physicians in enrolling patients to genotype-matched IRB-approved clinical trials. The DCMS sends automated, actionable, and secure email notifications to users with information about eligible or enrolled patients before their upcoming appointments. The system also captures investigators input via annotations on patient eligibility and preferences on future status updates. As of August 2015, the DCMS is tracking 159,893 patients on both clinical operations and research cohorts. 134 research cohorts have been established and track 64,473 patients. 51,192 of these have had one or more genomic tests including MSK-IMPACT, comprising the pool eligible for genotype-matched studies. This paper describes the design and evolution of this Informatics solution.


Variability of interferon-λ induction and antiviral activity in Nipah virus infected differentiated human bronchial epithelial cells of two human donors.
Highly pathogenic Nipah virus (NiV) generally causes severe encephalitis in humans. Respiratory symptoms are infrequently observed, likely reflecting variations in infection kinetics in human airways. Supporting this idea, we recently identified individual differences in NiV replication kinetics in cultured airway epithelia from different human donors. As type III interferons (IFN-λ) represent major players in the defence mechanism against viral infection of the respiratory mucosa, we studied IFN-λ induction and antiviral activity in NiV-infected primary differentiated human bronchial epithelial cells (HBEpCs) cultured under air-liquid interface conditions. Our studies revealed that IFN-λ was upregulated in airway epithelia upon NiV infection. We also show that IFN-λ pretreatment efficiently inhibited NiV replication. Interestingly, the antiviral activity of IFN-λ varied in HBEpCs from two different donors. Increased sensitivity to IFN-λ was associated with higher expression levels of IFN-λ receptors, enhanced phosphorylation of STAT1, as well as enhanced induction of interferon-stimulated gene expression. These findings suggest that individual variations in IFN-λ receptor expression affecting IFN responsiveness can play a functional role for NiV replication kinetics in human respiratory epithelial cells of different donors.


Abnormal expression of mouse mast cell protease 5 gene in cultured mast cells derived from mutant mi/mi mice.
Mast cells contain a lot of mast cell-specific proteases. We have reported that the expression of mouse mast cell protease 6 (MMCP-6) is remarkably reduced in both cultured mast cells (CMCs) and skin mast cells of mi/mi mutant mice. In the present study, we found that the expression of MMCP-5 was reduced in CMCs but not in skin mast cells of mi/mi mice, and we compared the regulation mechanisms of MMCP-5 with those of MMCP-6. The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). The consensus sequence recognized and bound by bHLH-Zip transcription factors is CANNTG. The overexpression of the normal (+) MITF but not of mi-MITF normalized the poor expression of the MMCP-5 gene in mi/mi CMCs, indicating the involvement of +-MITF in transactivation of the MMCP-5 gene. Although +-MITF directly bound CANNTG motifs in the promoter region of the MMCP-6 gene and transactivated it, the binding of +-MITF to the CAGTTG motif in the promoter region of the MMCP-5 gene was not detectable. The +-MITF appeared to regulate the transactivation of the MMCP-5 gene indirectly. Moreover, addition of stem cell factor to the medium normalized the expression of the MMCP-5 but not of the MMCP-6 gene in mi/mi CMCs. Despite the significant reduction of both MMCP-5 and MMCP-6 expressions in mi/mi CMCs, their regulation mechanisms appeared to be different.


Maternal separation in rats leads to anxiety-like behavior and a blunted ACTH response and altered neurotransmitter levels in response to a subsequent stressor.
Adverse early life experiences can have a negative impact on behavior later in life. We subjected rat pups to maternal separation and determined the effect's thereof on adult behavior. We removed rat pups from their mothers for 3 h daily from postnatal days 2 to 14. While controls were reared normally on day 60, the behaviors of the rats were tested using the elevated plus-maze. Some rats were subsequently subjected to restraint stress for a 10-min period. Trunk blood was collected for basal, as well as 15- and 60-min postrestraint stress ACTH determinations. Neurotransmitter levels (noradrenaline (NA), serotonin (5HT), and their metabolites, MHPG and 5HIAA, respectively) were also determined at basal, immediately and 15-min post-restraint stress in the hypothalamus, hippocampus, and frontal cortex in another group of animals. The amount of entries into the arms of the elevated plus-maze was significantly reduced in the separated animals, indicating decreased locomotion. They spent significantly more time in the closed arms of the maze. A significant increase in defecation frequency was noted. These observations suggested anxious behavior. Basal ACTH levels were significantly higher in separated animals. At 15-min post-restraint stress, the ACTH levels were significantly lower than controls, indicating a blunted stress response. A decrease in noradrenaline was noted first in limbic regions and an increase in 5HIAA levels was found in the frontal cortex and hippocampus. We conclude that maternal separation induced abnormal behaviors and stress responses that were associated with altered neurotransmitter levels.


Electrical signalling and plant response to herbivory: A short review.
For a long time, electrical signaling was neglected at the expense of signaling studies in plants being concentrated with chemical and hydraulic signals. Studies conducted in recent years have revealed that plants are capable of emitting, processing, and transmitting bioelectrical signals to regulate a wide variety of physiological functions. Many important biological and physiological phenomena are accompanied by these cellular electrical manifestations, which supports the hypothesis about the importance of bioelectricity as a fundamental 'model' for response the stresses environmental and for activities regeneration of these organisms. Electrical signals have also been characterized and discriminated against in genetically modified plants under stress mediated by sucking insects and/or by the application of systemic insecticides. Such results can guide future studies that aim to elucidate the factors involved in the processes of resistance to stress and plant defense, thus aiding in the development of successful strategies in integrated pest management. Therefore, this mini review includes the results of studies aimed at electrical signaling in response to biotic stress. We also demonstrated how the generation and propagation of electrical signals takes place and included a description of how these electrical potentials are measured.


CNS effects of indomethacin: should patients be cautioned about decreased mental alertness and motor coordination?
In many European countries as well as in the USA, the leaflet, or even the packaging of indomethacin, contains a specific warning to refrain from activities requiring mental alertness and motor coordination, such as driving a car. In this placebo-controlled randomized study with a crossover design we attempted to find evidence for that warning. Indomethacin 75 mg slow release or a visually identical placebo with similar flavour was taken orally twice daily for 2.5 days. It was suggested that indomethacin affects the motor coordination required to avoid obstacles successfully during walking and that this effect will be even stronger when simultaneously performing a cognitive task that puts mental alertness to the test. Nineteen healthy middle-aged individuals (60 ± 4.7 years, eight female) performed an obstacle avoidance task on a treadmill), combined with a cognitive secondary task. Biceps femoris (BF) muscle response times, obstacle avoidance failure rates and composite scores ((100 × accuracy)/verbal response time) were used to evaluate the data. No differences between indomethacin and placebo were found on the outcome measures regarding motor coordination, avoidance failure rates (P = 0.81) and BF response times (P = 0.47), nor on the performance on the secondary cognitive task (P = 0.12). Even though surrogate methods were used, the current study provides evidence to suggest that there might be no need to caution patients who experience CNS side effects after indomethacin use to avoid activities requiring quick and adequate reactions, such as walking under challenging circumstances and maybe also driving a car.


Novel liquid chromatography-mass spectrometry method shows that vitamin E deficiency depletes arachidonic and docosahexaenoic acids in zebrafish (Danio rerio) embryos.
To test the hypothesis that embryogenesis depends upon α-tocopherol (E) to protect embryo polyunsaturated fatty acids (PUFAs) from lipid peroxidation, new methodologies were applied to measure α-tocopherol and fatty acids in extracts from saponified zebrafish embryos. A solid phase extraction method was developed to separate the analyte classes, using a mixed mode cartridge (reverse phase, π-π bonding, strong anion exchange), then α-tocopherol and cholesterol were measured using standard techniques, while the fatty acids were quantitated using a novel, reverse phase liquid chromatography-mass spectrometry (LC-MS) approach. We also determined if α-tocopherol status alters embryonic lipid peroxidation products by analyzing 24 different oxidized products of arachidonic or docosahexaenoic (DHA) acids in embryos using LC with hybrid quadrupole-time of flight MS. Adult zebrafish were fed E- or E+ diets for 4 months, and then were spawned to obtain E- and E+ embryos. Between 24 and 72 hours post-fertilization (hpf), arachidonic acid decreased 3-times faster in E- (21 pg/h) compared with E+ embryos (7 pg/h, P<0.0001), while both α-tocopherol and DHA concentrations decreased only in E- embryos. At 36 hpf, E- embryos contained double the 5-hydroxy-eicosatetraenoic acids and 7-hydroxy-DHA concentrations, while other hydroxy-lipids remained unchanged. Vitamin E deficiency during embryogenesis depleted DHA and arachidonic acid, and increased hydroxy-fatty acids derived from these PUFA, suggesting that α-tocopherol is necessary to protect these critical fatty acids.


Testing the validity of Northern European species in the Chrysis ignita species group (Hymenoptera: Chrysididae) with DNA barcoding.
Containing more than a hundred species, the Chrysis ignita species group is the largest and one of the most taxonomically challenging groups in its genus. It has not been possible to resolve the taxonomy of the group using traditional methods due to the lack of robust diagnostic morphological characters. Here we present the results of a molecular analysis designed to delimit species in the Chrysis ignita group for the first time; using mitochondrial sequence data for 364 in-group specimens consisting of all 18 species known to occur in Northern Europe. Two mitochondrial loci were analysed: a COI gene fragment, and a continuous DNA sequence consisting of 16S rRNA, tRNAVal, 12S rRNA and ND4. Two approaches were employed for delimiting species: (1) genetic distance analysis based on the standard COI barcode sequences and; (2) phylogenetic analysis of the COI fragment together with rRNA genes. Both analyses yielded trees with similar topology, but support values for nodes were higher using the second approach. Fifteen species were distinguished in all analyses: Chrysis angustula Schenck, 1856, C. brevitarsis Thomson, 1870, C. clarinicollis Linsenmaier, 1951, C. corusca Valkeila, 1971, C. fulgida Linnaeus, 1761, C. ignita (Linnaeus, 1758), C. impressa Schenck, 1856, C. iris Christ, 1791, C. leptomandibularis Niehuis, 2000, C. longula Abeille de Perrin, 1879, C. ruddii Shuckard, 1837, C. schencki Linsenmaier, 1968, C. subcoriacea Linsenmaier, 1959, C. terminata Dahlbom, 1854 and C. vanlithi Linsenmaier, 1959. The specific status of C. mediata Linsenmaier, 1951 and C. solida Haupt, 1957 was not resolved. Included unidentified specimens grouped in three clusters, two of which are distinctly delimited and apparently represent cryptic species. The specific status of the unidentified samples in the third cluster remained unclear. Moreover, our data suggest the existence of additional cryptic species currently lumped under the names C. pseudobrevitarsis Linsenmaier, 1951 and C. schencki Linsenmaier, 1968. In conclusion, our results derived from analysis of mitochondrial loci strongly support the specific status of the majority of currently recognised species in the Chrysis ignita species group, and suggest the existence of additional cryptic species in Northern Europe. Thus, considering the difficulties that often arise during species determination based on morphological characters, the mtDNA loci used here appear highly suitable for assisting species delimitation in this group as well as identification of specimens.


In vitro dedifferentiation of melanocytes from adult epidermis.
In previous work we described a novel culture technique using a cholera toxin and PMA-free medium (Mel-mix) for obtaining pure melanocyte cultures from human adult epidermis. In Mel-mix medium the cultured melanocytes are bipolar, unpigmented and highly proliferative. Further characterization of the cultured melanocytes revealed the disappearance of c-Kit and TRP-1 and induction of nestin expression, indicating that melanocytes dedifferentiated in this in vitro culture. Cholera toxin and PMA were able to induce c-Kit and TRP-1 protein expressions in the cells, reversing dedifferentiation. TRP-1 mRNA expression was induced in dedifferentiated melanocytes by UV-B irradiated keratinocyte supernatants, however direct UV-B irradiation of the cells resulted in further decrease of TRP-1 mRNA expression. These dedifferentiated, easily accessible cultured melanocytes provide a good model for studying melanocyte differentiation and possibly transdifferentiation. Because melanocytes in Mel-mix medium can be cultured with human serum as the only supplement, this culture system is also suitable for autologous cell transplantation.


A Caenorhabditis elegans type I TGF beta receptor can function in the absence of type II kinase to promote larval development.
The daf-4 gene encodes a type II bone morphogenetic protein receptor in Caenorhabditis elegans that regulates dauer larva formation, body size and male tail patterning. The putative type I receptor partner for DAF-4 in regulating dauer larva formation is DAF-1. Genetic tests of the mechanism of activation of these receptors show that DAF-1 can signal in the absence of DAF-4 kinase activity. A daf-1 mutation enhances dauer formation in a daf-4 null background, whereas overexpression of daf-1 partially rescues a daf-4 mutant. DAF-1 alone cannot fully compensate for the loss of DAF-4 activity, indicating that nondauer development normally results from the activities of both receptors. DAF-1 signaling in the absence of a type II kinase is unique in the type I receptor family. The activity may be an evolutionary remnant, owing to daf-1's origin near the type I/type II divergence, or it may be an innovation that evolved in nematodes. daf-1 and daf-4 promoters both mediated expression of green fluorescent protein in the nervous system, indicating that a DAF-1/DAF-4 receptor complex may activate a neuronal signaling pathway. Signaling from a strong DAF-1/DAF-4 receptor complex or a weaker DAF-1 receptor alone may provide larvae with more precise control of the dauer/nondauer decision in a range of environmental conditions.


[Miller Fisher syndrome: review of the literature and presentation of 2 cases].
Miller Fisher Syndrome (MFS), which is characterized by ophthalmoplegia, ataxia and tendon areflexia, is generally considered as a clinical variant of Guillain-Barré Syndrome. However some features of the disease are still debated, particularly regarding possible central nervous system involvement. After presenting two new cases of MFS, the authors provide a critical review of the literature and discuss the nosographical position of the disease. The main conclusions can be summarized as follows: MFS is a predominantly axonal inflammatory neuropathy with prevailing involvement of oculomotor nerves. It is associated to spinal multi or polyneuropathy, which in mildly affected cases is manifested by areflexia, while in severe ones it can be responsible of sense and/or motor impairment. In addition to peripheral neuropathy CNS involvement, exclusive or more marked in posterior fossa, occurs not infrequently. The prognosis of the disease is often benign, but disabling or even fatal outcome is possible. Corticosteroid treatment, possibly because of antiinflammatory and/or immunosuppressive action, could be effective in some patients. Finally, in spite of some similarities with GBS, MFS should be considered as a separate entity with its own nosographical position.


Activation of cannabinoid receptor type 1 impairs spatial and temporal aspects of episodic-like memories in rats.
The endocannabinoid system modulates many brain functions, including episodic memories, which contain memories of time and places. Most studies have focused on the involvement of the endocannabinoid system in spatial memory; however, its role in temporal memory is not well understood. Few studies have tested whether the unilateral endocannabinoid system is sufficient to modulate memory retrieval. Here, we tested whether type 1 cannabinoid receptors in the right hippocampal cornu ammonis area 1 region are enough to modulate the retrieval of episodic memories, specifically their spatial and temporal components. Because rats have innate preferences for displaced or old familiar objects, we changed the locations of "old familiar" and "recent familiar" objects in an open field and measured the rats' exploration times to evaluate spatial and temporal memory. To address the influence of the type 1 cannabinoid receptors on the retrieval of episodic-like memories, two doses of arachidonylcyclopropylamide, a selective type 1 cannabinoid receptor agonist, were infused into the cornu ammonis area 1 of rats ten minutes before the discrimination trials. We observed that rats injected with a low dose of arachidonylcyclopropylamide spent less time investigating displaced objects, suggesting spatial memory impairment, whereas those receiving a high dose explored old familiar objects less frequently, suggesting temporal memory impairment. This indicates that unilateral activation of type 1 cannabinoid receptors in the cornu ammonis area 1 impairs the spatial and temporal aspects of episodic memories. This research mimics the influence of marijuana intoxication effects in humans, such as spatial and temporal disintegration.


Bilateral dorsal fronto-parietal areas are associated with integration of visual motion information and timed motor action.
Interaction with the environment often involves situations requiring visuomotor integration. For instance, in fast interceptive actions, the brain must integrate visual information of motion with the appropriate motor action. In such dynamic situation, the brain may control movement based on predictions of where the object will be in the future and when it will arrive there. Although previous studies have analyzed brain regions associated with processing visual information of motion, motor control and visuomotor integration with static objects, less is known about visuomotor integration with moving objects. In the present study we used an event-related fMRI experiment to investigate brain areas integrating visual information of motion with motor action in response to moving objects. Twenty healthy volunteers performed an interceptive task where they had to press a button in synchrony with the arrival of a horizontally moving target at a predefined location. They also performed two control tasks-simple reaction and attention to visual motion-in order to identify and exclude brain areas that would be involved in motor or visual motion processing components that are inherent to interceptive tasks. Through a conjunction analysis, we show greater BOLD signal in a bilateral dorsal fronto-parietal network, as well as the intraparietal sulcus, angular gyrus, and human visual motion area hV5+. We discuss these results with respect to their previously identified functions, and suggest they play a role in visuomotor integration with moving objects.


Pre-eclampsia/eclampsia in twin pregnancies.
A study of 1045 twin gestations with regard to known or likely zygosity and the incidence of pre-eclampsia/eclampsia failed to reveal differences between known dizygous twins and like-sex 'presumed' and 'estimated' monozygous twins except in the 'estimated' data for multigravidae. There was a threefold increase in the incidence for twins as opposed to singleton pregnancies. These results are discussed in relation to increased conceptus-mother antigenic differences. It is suggested that the risk of gestosis in twin pregnancy involves more than a summation of that operating in two singleton pregnancies.


The dietary n6:n3 fatty acid ratio during pregnancy is inversely associated with child neurodevelopment in the EDEN mother-child cohort.
Long-chain polyunsaturated fatty acids (LC-PUFAs) of the n6 (ω6) and n3 series are essential for the development of a child's brain. Fetal LC-PUFA exposure as well as infant exposure via breast milk depend on the maternal intake of these LC-PUFAs and of their respective dietary precursors (PUFAs). We aimed to investigate the associations between maternal LC-PUFA and PUFA [(LC)PUFA] dietary intake during pregnancy and child neurodevelopment at ages 2 and 3 y. In 1335 mother-child pairs from the EDEN cohort, we evaluated associations between daily maternal (LC)PUFA intake during the last 3 months of pregnancy with the child's language at age 2 y and with different assessments of development at age 3 y. Associations were investigated separately in breastfed and never-breastfed children. We examined interactions between the ratios of n6 and n3 (LC)PUFA intakes (n6:n3 fatty acid ratio) and duration of breastfeeding. Breastfeeding mothers had a lower n6:n3 fatty acid ratio (8.4 vs. 8.8; P = 0.02). Among never-breastfed children (n = 338), we found negative associations between maternal dietary n6:n3 fatty acid ratios and neurodevelopment, as reflected by the child's language at age 2 y (β ± SE = -2.1 ± 0.7; P = 0.001) and development assessed with the Ages and Stages Questionnaire at age 3 y (-1.5 ± 0.8; P = 0.05). Among mothers with a high n6:n3 fatty acid ratio only, breastfeeding duration was positively associated with language at age 2 y (P-interaction < 0.05). This suggests that the ratio between maternal dietary n6 and n3 (LC)PUFA intake possibly influences the child's brain development during fetal life but not during or by breastfeeding. However, breastfeeding might compensate for prenatal imbalance in maternal dietary n6:n3 fatty acid ratio.


Effect of dihydromyricetin on benzo[a]pyrene activation in rats.
Flavanol dihydromyricetin (DHM) has been shown to counteract acute ethanol (EtOH) intoxication and reduce excessive EtOH consumption. Since this flavonoid is being considered for human use, the in vivo study of DHM interactions with the cytochrome P450 (CYP) multienzyme system in the respect of metabolic activation of a model food-born carcinogen, benzo[a]pyrene (BaP), is of high importance. Flavonoids of known properties, alpha-naphthoflavone (ANF) and beta-naphthoflavone (BNF) were included into the study to compare their and DHM effects on BaP-DNA adduct formation. METH0 DS: The flavonoids were administered by oral gavage either 72 hrs prior or simultaneously with a single dose of BaP to experimental rats. The expression of CYP1A1/2 enzymes was examined based on the enzymatic activity with a marker substrate, 7-ethoxyresorufin, and on Western blots. The nuclease P1 version of the 32P-postlabeling assay was used to detect and quantify covalent DNA adducts formed by BaP. Treatment of rats with a single dose of DHM or ANF prior to or simultaneously with BaP did not produce an increase in levels of CYP1A1 and in formation of BaP-DNA adducts in liver. BNF, a known inducer of CYP1A1, showed a synergistic effect on BaP-mediated CYP1A1 induction and BaP activation in liver. Contrary to that, in small intestine the stimulatory effect of BNF on both parameters was not detected. Animal pre-treatment with DHM or ANF before BaP administration resulted in a significant elevation of BaP-DNA adducts, namely in the distal part of small intestine, while the CYP1A1 mediated 7-ethoxyresorufin-O-deethylation (EROD) was decreased markedly. It is important to note that under all regimens of animal treatment, DHM or ANF produced the higher inhibitory effect on the BaP-DNA adduct formation and BaP-induced EROD activity of CYP1A1 when administered simultaneously than sequentially with BaP. Our data show that DHM or ANF did not enhance the BaP-activation leading to BaP-mediated genotoxicity (the formation of BaP-DNA adducts) in rat liver, however, in small intestine the pretreatment of rats with these flavonoids may enhance BaP genotoxicity. The data indicate that the intake of DHM prior to or simultaneously with the administration of BaP may increase the risk of a BaP-induced tumorigenesis in small intestine.


Acceleration of protease effect on Staphylococcus aureus biofilm dispersal.
Bacterial biofilms are associated with the persistent infections because of their high tolerance to antimicrobial agents. Hence, controlling pathogenic biofilm formation is important in bacteria-related diseases. Staphylococcus aureus is a versatile human pathogen that readily forms biofilms on human tissues and diverse medical devices. As S. aureus can be naturally found in multi-species communities, the supernatants of 28 bacteria were screened to identify new biofilm inhibitory components against S. aureus. The culture supernatant (1%, v/v) of Pseudomonas aeruginosa PAO1 inhibited S. aureus biofilm formation more than 90% without affecting its planktonic cell growth. The P. aeruginosa supernatant contained a high protease activity, which both inhibited S. aureus biofilm formation and detached pre-existing biofilms. An examination of 13 protease-deficient P. aeruginosa mutants identified that LasB elastase is a major antibiofilm protease in P. aeruginosa against S. aureus. Transcriptional analyses showed that P. aeruginosa supernatant induced the expression of endogenous protease genes (aur, clp, scpA, splA, and sspA) and other regulatory genes (agrA, hla, and saeS). Additionally, exogenous proteinase K clearly enhanced the protease activity of S. aureus. Hence, S. aureus accelerated the expression of its own protease genes in the presence of exogenous protease, leading to the rapid dispersal of its biofilm.


Generation of Patient-Specific Cardiac Vascular Networks: A Hybrid Image-Based and Synthetic Geometric Model.
In this paper, we propose an algorithm for the generation of a patient-specific cardiac vascular network starting from segmented epicardial vessels down to the arterioles. We extend a tree generation method based on satisfaction of functional principles, named constrained constructive optimization, to account for multiple, competing vascular trees. The algorithm simulates angiogenesis under vascular volume minimization with flow-related and geometrical constraints adapting the simultaneous tree growths to patient priors. The generated trees fill the entire left ventricle myocardium up to the arterioles. From actual vascular tree models segmented from CT images, we generated networks with 6000 terminal segments for six patients. These networks contain between 33 and 62 synthetic trees. All vascular models match morphometry properties previously described. Image-based models derived from CT angiography are being used clinically to simulate blood flow in the coronary arteries of individual patients to aid in the diagnosis of disease and planning treatments. However, image resolution limits vessel segmentation to larger epicardial arteries. The generated model can be used to simulate the blood flow and derived quantities from the aorta into the myocardium. This is an important step for diagnosis and treatment planning of coronary artery disease.


Recent adaptive selection at MAOB and ancestral susceptibility to schizophrenia.
The ancestral susceptibility hypothesis has been proposed to explain the existence of susceptibility alleles to common diseases. Some ancestral alleles, reflecting ancient adaptations, may be poorly adapted to the more contemporary environmental conditions giving rise to an increased risk to suffer some common disorders. In order to test this hypothesis in schizophrenia, we focused on the monoamine oxidase B gene (MAOB). This gene is involved in deamination of several monoamines, including both xenobiotic amines present in several foods, as well as neurotransmitters such as dopamine. In addition, preliminary analysis based on phase I HapMap data suggested that recent natural selection has acted on this locus. We further explored the existence of this recent positive selection using a test based on extension of linkage disequilibrium (LD) to large distance at the specific selected haplotype taking data from HapMap phase II, and searched for association of the ancestral haplotypes with schizophrenia in a sample of 532 schizophrenic patients and 597 controls from Spain. Our analysis suggested the existence of a haplotype of MAOB subject to recent selection. In agreement with the ancestral susceptibility hypothesis, the ancestral haplotypes were significantly over-represented in patients (P = 0.047). These haplotypes conferred an increased risk to schizophrenia, restricted to males (P = 0.024, OR = 1.41, 95% CI 1.01-1.90). Thus, pending on replication studies, MAOB seems to fit the ancestral susceptibility model, validating a new strategy to search for common schizophrenia susceptibility genes by focusing in those functional candidate genes subject to recent positive selection.


Redefining ultrasound appearance criteria of positive axillary lymph nodes.
To determine objective criteria for ultrasonography (US) appearance in the diagnosis of abnormal axillary lymph nodes (ALNs) and to assess retrospectively their accuracy in preoperative staging of patients with Breast Imaging Reporting and Data System (BI-RADS) Category 5 breast lesion. US-guided axillary fine-needle aspiration biopsy (FNAB) was performed for preoperative staging of BI-RADS Category 5 lesions in breast cancer patients seen at the Ottawa Regional Women's Breast Health Centre. Retrospectively, ALN morphology was classified into 3 categories based on US appearance: mass-like appearance, focal nodular cortical thickening (FNCT), and diffuse cortical thickening (DCT), the latter 2 with fatty hilum preservation and cortical thickening greater than 2 mm. Cytologic results from the FNAB were compared with axillary lymph node dissection (ALND) or sentinel lymph node procedure (SLNP), when available. Retrospective image-based classification was performed blind to pathology results and analyzed with Pearson's correlation coefficient, receiver operating characteristic (ROC) curves, and chi-square and Hosmer-Lemeshow tests against the cytologic ground truth. Eighty-six ALNs in 84 patients were sampled with an 18-gauge needle under US guidance. The number of passes per sample was related to adequate sampling of positive ALNs having mass-like morphology but not DCT or FNCT (p < 0.001). The most frequent morphologic presentation of the 86 ALNs was mass-like appearance of lymph nodes (45%), followed by DCT (35%) and FNCT (20%). Metastatic involvement was found in 34 (87%) of 39 ALNs that were mass-like, in 9 (53%) of 17 ALNs with FNCT, and in 9 (30%) of 30 ALNs with DCT. The kappa agreement between FNAB and ALND or SLNP was 0.64 for mass-like lymph nodes, 0.7 for lymph nodes with DCT, and 1.0 for FNCT. Overall sensitivity and specificity were 94% and 89%, respectively, with a positive predictive value of 97% and negative predictive value of 80%. Using a 2-mm threshold, FNCT and DCT warrant US-guided FNAB by an experienced radiologist as much as do mass-like lymph nodes. When biopsy is positive, axillary dissection can be performed and the sentinel node technique avoided.


An Evaluation of Severe Anesthetic-Related Critical Incidents and Risks From the South African Paediatric Surgical Outcomes Study: A 14-Day Prospective, Observational Cohort Study of Pediatric Surgical Patients.
Severe anesthetic-related critical incident (SARCI) monitoring is an essential component of safe, quality anesthetic care. Predominantly retrospective data from low- and middle-income countries (LMICs) report higher incidence but similar types of SARCI compared to high-income countries (HIC). The aim of our study was to describe the baseline incidence of SARCI in a middle-income country (MIC) and to identify associated risk for SARCI. We hypothesized a higher incidence but similar types of SARCI and risks compared to HICs. We performed a 14-day, prospective multicenter observational cohort study of pediatric patients (aged <16 years) undergoing surgery in government-funded hospitals in South Africa, a MIC, to determine perioperative outcomes. This analysis described the incidence and types of SARCI and associated perioperative cardiac arrests (POCAs). We used multivariable logistic regression analysis to identify risk factors independently associated with SARCI, including 7 a priori variables and additional candidate variables based on their univariable performance. Two thousand and twenty-four patients were recruited from May 22 to August 22, 2017, at 43 hospitals. The mean age was 5.9 years (±standard deviation 4.2). A majority of patients during this 14-day period were American Society of Anesthesiologists (ASA) physical status I (66.4%) or presenting for minor surgery (54.9%). A specialist anesthesiologist managed 59% of cases. These patients were found to be significantly younger (P < .001) and had higher ASA physical status (P < .001). A total of 426 SARCI was documented in 322 of 2024 patients, an overall incidence of 15.9% (95% confidence interval [CI], 14.4-17.6). The most common event was respiratory (214 of 426; 50.2%) with an incidence of 8.5% (95% CI, 7.4-9.8). Six children (0.3%; 95% CI, 0.1-0.6) had a POCA, of whom 4 died in hospital. Risks independently associated with a SARCI were age (adjusted odds ratio [aOR] = 0.95; CI, 0.92-0.98; P = .004), increasing ASA physical status (aOR = 1.85, 1,74, and 2.73 for ASA II, ASA III, and ASA IV-V physical status, respectively), urgent/emergent surgery (aOR = 1.35, 95% CI, 1.02-1.78; P = .036), preoperative respiratory infection (aOR = 2.47, 95% CI, 1.64-3.73; P < .001), chronic respiratory comorbidity (aOR = 1.75, 95% CI, 1.10-2.79; P = .018), severity of surgery (intermediate surgery aOR = 1.84, 95% CI, 1.39-2.45; P < .001), and level of hospital (first-level hospitals aOR = 2.81, 95% CI, 1.60-4.93; P < .001). The incidence of SARCI in South Africa was 3 times greater than in HICs, and an associated POCA was 10 times more common. The risk factors associated with SARCI may assist with targeted interventions to improve safety and to triage children to the optimal level of care.


The Association Between Educational Attainment and Diabetes Among Men in the United States.
Few studies have examined the relationship between education and diabetes among men in the United States and whether this relationship differs by race/ethnicity. This study examined whether racial disparities in diabetes existed by educational attainment in 336,746 non-Hispanic White, non-Hispanic Black, and Hispanic men 18 years of age and older in the United States. Logistic regression models were specified to examine the odds of reporting diabetes by educational attainment. Within race/ethnicity, both White and Hispanic men who had less than a high school education (odds ratio [OR] = 1.42, 95% confidence interval [CI] = [1.19, 1.69], and OR = 1.64, 95% CI = [1.22, 2.21], respectively) had consistently higher odds of diabetes than men with a bachelor's degree or higher level of educational attainment. Educational attainment did not appear to be associated with reporting a diagnosis of diabetes in non-Hispanic Black men. Identifying why educational attainment is associated with diabetes outcomes in some racial/ethnic groups but not others is essential for diabetes treatment and management.


Polyphthalaldehyde-block-polystyrene as a nanochannel template.
A degradable polyphthalaldehyde-polystyrene block copolymer generated by modular ligation is reported for the first time serving as a nanochannel template for the formation of nanostructured materials. The polyphthalaldehyde-b-polystyrene copolymer was spin-coated onto a surface with subsequent polyphthalaldehyde block removal. Block conjugation and block removal were confirmed by H-NMR, SEC, AFM, and SEM.


Exploring the Early Stages of the Amyloid Aβ(1-42) Peptide Aggregation Process: An NMR Study.
Alzheimer's disease (AD) is a neurodegenerative pathology characterized by the presence of neurofibrillary tangles and amyloid plaques, the latter mainly composed of Aβ(1-40) and Aβ(1-42) peptides. The control of the Aβ aggregation process as a therapeutic strategy for AD has prompted the interest to investigate the conformation of the Aβ peptides, taking advantage of computational and experimental techniques. Mixtures composed of systematically different proportions of HFIP and water have been used to monitor, by NMR, the conformational transition of the Aβ(1-42) from soluble α-helical structure to β-sheet aggregates. In the previous studies, 50/50 HFIP/water proportion emerged as the solution condition where the first evident Aβ(1-42) conformational changes occur. In the hypothesis that this solvent reproduces the best condition to catch transitional helical-β-sheet Aβ(1-42) conformations, in this study, we report an extensive NMR conformational analysis of Aβ(1-42) in 50/50 HFIP/water v/v. Aβ(1-42) structure was solved by us, giving evidence that the evolution of Aβ(1-42) peptide from helical to the β-sheet may follow unexpected routes. Molecular dynamics simulations confirm that the structural model we calculated represents a starting condition for amyloid fibrils formation.


Interleukin family member ST2 and mortality in acute dyspnoea.
The study objective was to investigate the prognostic utility and patient-specific characteristics of ST2 (suppression of tumorigenicity 2), assessed with a novel sensitive assay. Suppression of tumorigenicity 2 signalling has been shown to be associated with death in cardiac and pulmonary diseases. In an international multicentre cohort design, we prospectively enrolled 1091 patients presenting with acute dyspnoea to the emergency department (ED). ST2 was measured in a blinded fashion using a novel assay and compared to B-type natriuretic peptide (BNP) and NT-proBNP. The primary end-point was mortality within 30 days and 1 year. The prognostic value of ST2 was evaluated in comparison and in addition to BNP and NT-proBNP. Suppression of tumorigenicity 2 concentrations was higher amongst decedents than among survivors (median 85 vs. 43 U mL⁻¹, P < 0.001) and also higher in patients with impaired left ventricular ejection fraction (LVEF) when compared with preserved LVEF (P < 0.001). In receiver operator characteristics analysis, the area under the curve (AUC) for ST2, BNP and NT-proBNP to predict 30-day and 1-year mortality were 0.76, 0.63 and 0.71, and 0.72, 0.71 and 0.73, respectively. The combinations of ST2 with BNP or NT-proBNP improved prediction of mortality provided by BNP or NT-proBNP alone. After multivariable adjustment, ST2 values above the median (50 U mL⁻¹) significantly predicted 1-year mortality (HR 2.3, P < 0.001). In patients presenting to the ED with acute dyspnoea, ST2 is a strong and independent predictor of 30-day and 1-year mortality and might improve risk stratification already provided by BNP or NT-proBNP.


Phylogeography of influenza A H5N1 clade 22.214.171.124 in Egypt.
Influenza A H5N1 has killed millions of birds and raises serious public health concern because of its potential to spread to humans and cause a global pandemic. While the early focus was in Asia, recent evidence suggests that Egypt is a new epicenter for the disease. This includes characterization of a variant clade 220.127.116.11, which has been found almost exclusively in Egypt.We analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 22.214.171.124 strains in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling of virus dispersion between Egyptian governorates including the most likely origin. Phylogeography models of hemagglutinin (HA) and neuraminidase (NA) suggest Ash Sharqiyah as the origin of virus spread, however the support is weak based on Kullback-Leibler values of 0.09 for HA and 0.01 for NA. Association Index (AI) values and Parsimony Scores (PS) were significant (p-value < 0.05), indicating that dispersion of H5N1 in Egypt was geographically structured. In addition, the Ash Sharqiyah to Al Gharbiyah and Al Fayyum to Al Qalyubiyah routes had the strongest statistical support. We found that the majority of routes with strong statistical support were in the heavily populated Delta region. In particular, the Al Qalyubiyah governorate appears to represent a popular location for virus transition as it represented a large portion of branches in both trees. However, there remains uncertainty about virus dispersion to and from this location and thus more research needs to be conducted in order to examine this.Phylogeography can highlight the drivers of H5N1 emergence and spread. This knowledge can be used to target public health efforts to reduce morbidity and mortality. For Egypt, future work should focus on using data about vaccination and live bird markets in phylogeography models to study their impact on H5N1 diffusion within the country.


Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis.
Disturbed folate metabolism is associated with an increased risk of some cancers. Our objective was to determine whether blood levels of folate, vitamin B(12), and related metabolites were associated with prostate cancer risk. Matched case-control study nested within the U.K. population-based Prostate testing for cancer and Treatment (ProtecT) study of prostate-specific antigen-detected prostate cancer in men ages 50 to 69 years. Plasma concentrations of folate, B(12) (cobalamin), holo-haptocorrin, holo-transcobalamin total transcobalamin, and total homocysteine (tHcy) were measured in 1,461 cases and 1,507 controls. ProtecT study estimates for associations of folate, B(12), and tHcy with prostate cancer risk were included in a meta-analysis, based on a systematic review. In the ProtecT study, increased B(12) and holo-haptocorrin concentrations showed positive associations with prostate cancer risk [highest versus lowest quartile of B(12) odds ratio (OR) = 1.17 (95% confidence interval, 0.95-1.43); P(trend) = 0.06; highest versus lowest quartile of holo-haptocorrin OR = 1.27 (1.04-1.56); P(trend) = 0.01]; folate, holo-transcobalamin, and tHcy were not associated with prostate cancer risk. In the meta-analysis, circulating B(12) levels were associated with an increased prostate cancer risk [pooled OR = 1.10 (1.01-1.19) per 100 pmol/L increase in B(12); P = 0.002]; the pooled OR for the association of folate with prostate cancer was positive [OR = 1.11 (0.96-1.28) per 10 nmol/L; P = 0.2) and conventionally statistically significant if ProtecT (the only case-control study) was excluded [OR = 1.18 (1.00-1.40) per 10 nmol/L; P = 0.02]. Vitamin B(12) and (in cohort studies) folate were associated with increased prostate cancer risk. Given current controversies over mandatory fortification, further research is needed to determine whether these are causal associations.


Semantic role labeling for protein transport predicates.
Automatic semantic role labeling (SRL) is a natural language processing (NLP) technique that maps sentences to semantic representations. This technique has been widely studied in the recent years, but mostly with data in newswire domains. Here, we report on a SRL model for identifying the semantic roles of biomedical predicates describing protein transport in GeneRIFs - manually curated sentences focusing on gene functions. To avoid the computational cost of syntactic parsing, and because the boundaries of our protein transport roles often did not match up with syntactic phrase boundaries, we approached this problem with a word-chunking paradigm and trained support vector machine classifiers to classify words as being at the beginning, inside or outside of a protein transport role. We collected a set of 837 GeneRIFs describing movements of proteins between cellular components, whose predicates were annotated for the semantic roles AGENT, PATIENT, ORIGIN and DESTINATION. We trained these models with the features of previous word-chunking models, features adapted from phrase-chunking models, and features derived from an analysis of our data. Our models were able to label protein transport semantic roles with 87.6% precision and 79.0% recall when using manually annotated protein boundaries, and 87.0% precision and 74.5% recall when using automatically identified ones. We successfully adapted the word-chunking classification paradigm to semantic role labeling, applying it to a new domain with predicates completely absent from any previous studies. By combining the traditional word and phrasal role labeling features with biomedical features like protein boundaries and MEDPOST part of speech tags, we were able to address the challenges posed by the new domain data and subsequently build robust models that achieved F-measures as high as 83.1. This system for extracting protein transport information from GeneRIFs performs well even with proteins identified automatically, and is therefore more robust than the rule-based methods previously used to extract protein transport roles.


An Online Tailored Self-Management Program for Patients With Rheumatoid Arthritis: A Developmental Study.
Every day rheumatoid arthritis (RA) patients make many decisions about managing their disease. An online, computer-tailored, self-management program can support this decision making, but development of such a program requires the active participation of patients. To develop an online, computer-tailored, self-management program integrated with the nursing care, as nurses have an important role in supporting self-management behavior. The intervention mapping framework was used to develop the program. Development was a multistep process: (1) needs assessment; (2) developing program and change objectives in a matrix; (3) selecting theory-based intervention methods and practical application strategies; (4) producing program components; (5) planning and adoption, implementation, and sustainability; and (6) planning for evaluation. After conducting the needs assessment (step 1), nine health-related problems were identified: (1) balancing rest and activity, (2) setting boundaries, (3) asking for help and support, (4) use of medicines, (5) communicating with health professionals, (6) use of assistive devices, (7) performing physical exercises, (8) coping with worries, and (9) coping with RA. After defining performance and change objectives (step 2), we identified a number of methods which could be used to achieve them (step 3), such as provision of general information about health-related behavior, self-monitoring of behavior, persuasive communication, modeling, and self-persuasion and tailoring. We described and operationalized these methods in texts, videos, exercises, and a medication intake schedule. The resulting program (step 4) consisted of an introduction module and nine modules dealing with health-related problems. The content of these modules is tailored to the user's self-efficacy, and patients can use the online program as often as they want, working through a module or modules at their own speed. After implementation (step 5), the program will be evaluated in a two-center pilot trial involving 200 RA patients. Log-in data and qualitative interviews will used for a process evaluation. The intervention mapping framework was used to guide development of an online computer-tailored self-management program via a process which could serve as a model for the development of other interventions. A pilot randomized controlled trial (RCT) will provide insight into the important outcome measures in preparation for a larger RCT. The process evaluation will provide insight into how RA patients use the program and the attrition rate. Netherlands Trial Register (NTR): NTR4871; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4871 [accessed 13-NOV-15] http://www.webcitation.org/6d1ZyIoEy.


Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD.
Inhaled corticosteroid-containing medications reduce the frequency of COPD exacerbations (mainly infectious in origin) while paradoxically increasing the risk of other respiratory infections. The aim was to determine the effects of inhaled corticosteroids on airway microbial load in COPD patients and evaluate the influence of the underlying inflammatory profile on airway colonisation and microbiome.This is a proof-of-concept prospective, randomised, open-label, blinded endpoint study. Sixty patients with stable moderate COPD were randomised to receive one inhalation twice daily of either a combination of salmeterol 50 μg plus fluticasone propionate 500 μg or salmeterol 50 μg for 12 months. The primary outcome was the change of sputum bacterial loads over the course of treatment.Compared with salmeterol, 1-year treatment with salmeterol plus fluticasone was associated with a significant increase in sputum bacterial load (p=0.005), modification of sputum microbial composition and increased airway load of potentially pathogenic bacteria. The increased bacterial load was observed only in inhaled corticosteroid-treated patients with lower baseline sputum or blood eosinophil (≤2%) levels but not in patients with higher baseline eosinophils.Long-term inhaled corticosteroid treatment affects bacterial load in stable COPD. Lower eosinophil counts are associated with increased airway bacterial load.


Do prostanoids or nitric oxide mediate sensitization of the von Bezold-Jarisch reflex by B-type natriuretic peptide?
1. Cardiac natriuretic peptides act on cardiopulmonary chemoreceptor afferents to enhance the von Bezold-Jarisch reflex (BJR). Activity of the natriuretic peptide particulate guanylyl cyclase receptor is essential for full expression of the BJR. Whether natriuretic peptides act directly on cardiac afferents or they require another intermediate factor(s) for their effects on the BJR is unknown. Endogenous candidates tested as possible intermediates in the present study were prostanoids and nitric oxide (NO), plausible endogenous chemical mediators of cardiac chemoreflex activity. 2. Dose-dependent BJR bradycardia was evoked by the 5-HT(3) receptor agonist, phenylbiguanide (range 5-89 μg/kg), in conscious instrumented adult sheep (n = 6). The influence of B-type natriuretic peptide (BNP; the most potent of the natriuretic peptides) on the BJR was assessed before and after blockade of prostanoids (using indomethacin, 1 mg/kg per h i.v.) or nitric oxide (using N-nitro-l-arginine (NOLA), 3 mg/kg bolus, then 3 mg/kg per h infusion i.v.). 3. On their own, indomethacin and NOLA did not significantly alter the BJR, showing that prostanoids and NO are not essential endogenous mediators of the BJR. As shown in previous studies, BNP (10 pmol/kg per min i.v.) infusion enhanced the BJR by 85 ± 36%, P < 0.05. When the production of either prostanoids or nitric oxide was inhibited, BNP still enhanced the BJR. 4. The present study provides evidence that BNP does not require the activity or influence of prostaglandins or NO for its sensitising effects on the BJR. We propose that natriuretic peptides act directly on cardiac afferents, in synergy with 5-HT(3) agonists, to facilitate the BJR.


Ultrasound in the assessment of cranial bone thickness.
Preoperative knowledge of skull thickness before harvesting cranial bone grafts would be ideal to help minimize intracranial complications. Previous research has demonstrated regional variations in calvaria; however, accurate preoperative and intraoperative methods of skull thickness measurement are not available. The aim of this research represents the first attempt to examine the reliability of ultrasound to determine cranial bone thickness. Four previously studied calvarial sites were marked in 10 adult male cadaveric skulls. The individual points were insonified using an A-mode ultrasonic transducer operating in pulse-echo mode. The times of flight of the waves propagating in the bone samples were compared with caliper measurements. The mean difference in cranial bone thickness was 0.16 mm, with a standard deviation of 0.09 mm. Student's t-test failed to reveal any statistically significant differences between caliper and ultrasonic measurements (p = 0.569) and Pearson's correlation coefficient supported an extremely strong and positive relationship between the two modalities (r > 0.992). Multiple linear regression models predicted that calvarial thickness could be accurately predicted by ultrasound without consideration of cadaveric specimen or sampling point location (R2 = 0.988). The convergent values between ultrasonic and caliper measurements suggest that this modality can accurately and reliably determine skull thickness. A-mode ultrasound can have significant implications in guiding the harvest of in situ split cranial bone grafts, the placement of osseointegrated implants, skull anthropometrics, and related craniomaxillofacial applications.


Paraneoplastic neuromuscular disorders.
Paraneoplastic neurological disorders are rare autoimmune conditions that can affect any part of the nervous system, including the peripheral nervous system. These disorders are associated with certain types of cancer, and the peripheral nervous system dysfunction often precedes the symptoms from the cancer itself. This investigation was undertaken as a topic review. Learning to recognize paraneoplastic neuromuscular disorders, the associated antibodies and their implications, and the appropriate screening modalities can, in some cases, lead to an earlier diagnosis of cancer. Eliminating the cancer, if present, and immunomodulation can potentially improve the symptoms and clinical outcome.


The biomechanical response of persons with transfemoral amputation to variations in prosthetic knee alignment during level walking.
Prosthetic alignment is an important factor in the overall fit and performance of a lower-limb prosthesis. However, the association between prosthetic alignment and control strategies used by persons with transfemoral amputation to coordinate the movement of a passive prosthetic knee is poorly understood. This study investigated the biomechanical response of persons with transfemoral amputation to systematic perturbations in knee joint alignment during a level walking task. Quantitative gait data were collected for three alignment conditions: bench alignment, 2 cm anterior knee translation (ANT), and 2 cm posterior knee translation (POST). In response to a destabilizing alignment perturbation (i.e., the ANT condition), participants significantly increased their early-stance hip extension moment, confirming that persons with transfemoral amputation rely on a hip extensor strategy to maintain knee joint stability. However, participants also decreased the rate at which they loaded their prosthesis, decreased their affected-side step length, increased their trunk flexion, and maintained their prosthesis in a more vertical posture at the time of opposite toe off. Collectively, these results suggest that persons with transfemoral amputation rely on a combination of strategies to coordinate stance-phase knee flexion. Further, comparatively few significant changes were observed in response to the POST condition, suggesting that a bias toward posterior alignment may have fewer implications in terms of stance-phase, knee joint control.


Clinical Analysis and Management of Acquired Idiopathic Generalized Anhidrosis.
Acquired idiopathic generalized anhidrosis (AIGA) is a sweating disorder characterized by inadequate sweating in response to heat stimuli such as high temperature, humidity, and physical exercise. Patients exhibit widespread nonsegmental hypohidrosis/anhidrosis without any apparent cause, but the palms, soles, and axillae are rarely affected. Heat stroke readily develops due to increased body temperature. AIGA commonly affects young males. Approximately 30-60% of patients show complications of cholinergic urticaria, also known as idiopathic pure sudomotor failure or hypohidrotic cholinergic urticaria. Systemic corticosteroids are the most effective therapy, although recurrence is not uncommon.


Gene Expression Noise Produces Cell-to-Cell Heterogeneity in Eukaryotic Homologous Recombination Rate.
Variation in gene expression among genetically identical individual cells (called gene expression noise) directly contributes to phenotypic diversity. Whether such variation can impact genome stability and lead to variation in genotype remains poorly explored. We addressed this question by investigating whether noise in the expression of genes affecting homologous recombination (HR) activity either directly (RAD52) or indirectly (RAD27) confers cell-to-cell heterogeneity in HR rate in Saccharomyces cerevisiae. Using cell sorting to isolate subpopulations with various expression levels, we show that spontaneous HR rate is highly heterogeneous from cell-to-cell in clonal populations depending on the cellular amount of proteins affecting HR activity. Phleomycin-induced HR is even more heterogeneous, showing that RAD27 expression variation strongly affects the rate of recombination from cell-to-cell. Strong variations in HR rate between subpopulations are not correlated to strong changes in cell cycle stage. Moreover, this heterogeneity occurs even when simultaneously sorting cells at equal expression level of another gene involved in DNA damage response (BMH1) that is upregulated by DNA damage, showing that the initiating DNA damage is not responsible for the observed heterogeneity in HR rate. Thus gene expression noise seems mainly responsible for this phenomenon. Finally, HR rate non-linearly scales with Rad27 levels showing that total amount of HR cannot be explained solely by the time- or population-averaged Rad27 expression. Altogether, our data reveal interplay between heterogeneity at the gene expression and genetic levels in the production of phenotypic diversity with evolutionary consequences from microbial to cancer cell populations.


Proposed method of measuring the current distribution in a tokamak plasma.
It is shown that the current distribution in a typical Tokamak plasma can be measured by a light scattering technique. The direction of the total magnetic field is measured accurately enough that the magnitude of the small poloidal component can be found. The field direction is measured by observing the scattered frequency spectrum of CO(2) laser light. The usual Gaussian spectrum becomes modulated at the electron cyclotron frequency when the difference between the incident and scattered wave vectors is nearly perpendicular to the magnetic field. The harmonics can be superimposed with a Fabry-Perot interferometer and their collective width resolved as the scattering direction is changed. The SNR is high only when the detector is shielded against background radiation.


A viral genome packaging ring-ATPase is a flexibly coordinated pentamer.
Multi-subunit ring-ATPases carry out a myriad of biological functions, including genome packaging in viruses. Though the basic structures and functions of these motors have been well-established, the mechanisms of ATPase firing and motor coordination are poorly understood. Here, using single-molecule fluorescence, we determine that the active bacteriophage T4 DNA packaging motor consists of five subunits of gp17. By systematically doping motors with an ATPase-defective subunit and selecting single motors containing a precise number of active or inactive subunits, we find that the packaging motor can tolerate an inactive subunit. However, motors containing one or more inactive subunits exhibit fewer DNA engagements, a higher failure rate in encapsidation, reduced packaging velocity, and increased pausing. These findings suggest a DNA packaging model in which the motor, by re-adjusting its grip on DNA, can skip an inactive subunit and resume DNA translocation, suggesting that strict coordination amongst motor subunits of packaging motors is not crucial for function.


Genetic diversity of human parvovirus B19 determined using a set of restriction endonucleases recognizing four or five base pairs and partial nucleotide sequencing: use of sequence variability in virus classification.
Analysis of the restriction site polymorphism (RSP) of human parvovirus B19 using 12 restriction endonucleases (REs) recognizing four or five bp sequences (4- or 5-bp REs) revealed a significant difference between strains previously classified as being of the same genome type, and a relationship between two strains of different genome types, thereby indicating a global spread of B19 virus strains. These findings demonstrate the advantage of this set of 4- and 5-bp REs for the calculation of the degree of genetic diversity and clearly it is necessary to amend the taxonomy of B19 virus strains using these REs. We examined the nucleotide (nt) sequence between nt 3141 and 3411, at the N terminus of the VP2 protein coding region, in 12 B19 virus strains. The pattern of distribution of nucleotide differences between the strains confirmed the classification by RSP analysis. Between nt 3293 and nt 3364, a region in which an antigenic epitope may be encoded, there was no evidence of a nucleotide change causing an amino acid change. Thus, the amino acid sequence in this potential epitope is probably conserved.


The public hospital in American medical education.
The importance of the public hospital system to medical education is often absent from the debate about its value. Best known as a core provider of services to the underserved, the safety net hospital system also plays a critical role in the education of future physicians. Particular strengths include its ability to imbue physicians in training with core professional values, to reveal through the enormous range of clinical experience provided many of the social forces shaping health, and to foster interest in and commitment to advancing population health. Faculty teaching in the public hospital system has unusual opportunities to reveal to learners the broader meanings of their diverse and rich experiences. Now, as an alarming array of pressures bearing down on the safety net system threaten its stability, the potential negative impact on medical education, were it to shrink or be forced to change its essential mission, must be considered. As advocates of the safety net system marshal forces to rationalize its funding and support, its tremendous contribution to the training of physicians and other health care professionals must be clearly set forth to ensure that support for the public hospital system's health is appropriately broad based.


Childhood Maltreatment and Impulsivity: A Meta-Analysis and Recommendations for Future Study.
Both childhood maltreatment and impulsivity have been implicated in a broad array of negative public health outcomes and have been much studied in relation to each other. Characterizing this relationship, and the processes underlying it, are important for informing intervention efforts targeting this association and its psychopathological sequelae. The current review presented a systematic meta-analysis of the empirical literature on childhood maltreatment and impulsivity. In all, 55 eligible studies were identified and included in this review. General support was found for a positive association between childhood maltreatment, including its specific subtypes, and general trait impulsivity, with pooled effect sizes ranging from small in the case of childhood sexual abuse (OR = 1.59 [95% CI = 1.38-1.84]) to medium-to-large in the case of childhood emotional abuse (OR = 3.10 [95% CI = 2.27-4.23]). Support for a relationship between childhood maltreatment and laboratory-based measures of impulsive behavior was generally lacking. The current findings must be interpreted with a degree of caution, given several methodological limitations characterizing much of the empirical literature. Recommendations for addressing these limitations and directions for future research are provided.


[The aggregation ability of the plague microbe].
Hemoglobin enhances the aggregation of the plague bacillus in fluids (p > 0.99), the proportion of its action on this process being 46.7%. The aggregated forms of the plague bacillus as conglomerates are of greater value in the virulence of the plague bacillus for white mice than are a series of plague bacilli or single microbes, which is an important factor in the mechanism of bacillus transmission. Block is an aggregated status of the plague bacillus in the gizzard of an effective vector.


The SKMT Algorithm: A method for assessing and comparing underlying protein entanglement.
We present fast and simple-to-implement measures of the entanglement of protein tertiary structures which are appropriate for highly flexible structure comparison. These are performed using the SKMT algorithm, a novel method of smoothing the Cα backbone to achieve a minimal complexity curve representation of the manner in which the protein's secondary structure elements fold to form its tertiary structure. Its subsequent complexity is characterised using measures based on the writhe and crossing number quantities heavily utilised in DNA topology studies, and which have shown promising results when applied to proteins recently. The SKMT smoothing is used to derive empirical bounds on a protein's entanglement relative to its number of secondary structure elements. We show that large scale helical geometries dominantly account for the maximum growth in entanglement of protein monomers, and further that this large scale helical geometry is present in a large array of proteins, consistent across a number of different protein structure types and sequences. We also show how these bounds can be used to constrain the search space of protein structure prediction from small angle x-ray scattering experiments, a method highly suited to determining the likely structure of proteins in solution where crystal structure or machine learning based predictions often fail to match experimental data. Finally we develop a structural comparison metric based on the SKMT smoothing which is used in one specific case to demonstrate significant structural similarity between Rossmann fold and TIM Barrel proteins, a link which is potentially significant as attempts to engineer the latter have in the past produced the former. We provide the SWRITHE interactive python notebook to calculate these metrics.


Functions of S100 proteins.
The S100 protein family consists of 24 members functionally distributed into three main subgroups: those that only exert intracellular regulatory effects, those with intracellular and extracellular functions and those which mainly exert extracellular regulatory effects. S100 proteins are only expressed in vertebrates and show cell-specific expression patterns. In some instances, a particular S100 protein can be induced in pathological circumstances in a cell type that does not express it in normal physiological conditions. Within cells, S100 proteins are involved in aspects of regulation of proliferation, differentiation, apoptosis, Ca2+ homeostasis, energy metabolism, inflammation and migration/invasion through interactions with a variety of target proteins including enzymes, cytoskeletal subunits, receptors, transcription factors and nucleic acids. Some S100 proteins are secreted or released and regulate cell functions in an autocrine and paracrine manner via activation of surface receptors (e.g. the receptor for advanced glycation end-products and toll-like receptor 4), G-protein-coupled receptors, scavenger receptors, or heparan sulfate proteoglycans and N-glycans. Extracellular S100A4 and S100B also interact with epidermal growth factor and basic fibroblast growth factor, respectively, thereby enhancing the activity of the corresponding receptors. Thus, extracellular S100 proteins exert regulatory activities on monocytes/macrophages/microglia, neutrophils, lymphocytes, mast cells, articular chondrocytes, endothelial and vascular smooth muscle cells, neurons, astrocytes, Schwann cells, epithelial cells, myoblasts and cardiomyocytes, thereby participating in innate and adaptive immune responses, cell migration and chemotaxis, tissue development and repair, and leukocyte and tumor cell invasion.