[Effects of single-seed sowing on canopy microenvironment, photosynthetic characteristics and pod yield of peanut (Arachis hypogaca)].
The large-seed peanut cultivar of Huayu 22 was used to study the differences of canopy microenvironment, photosynthetic characteristics, and pod yield at three single-seed sowing densities, i.e., 225000 (S₁), 195000 (S₂) and 165000 (S₃) holes per hectare, in field experiments. The results showed that the canopy light transmittance, canopy air temperature and canopy CO₂concentration all increased at these three single-seed sowing densities compared with those of double-seed sowing pattern (150000 holes per hectare), while the canopy humidity decreased. It seemed that single-seed sowing was helpful to improve microenvironment and the growth of peanut, especially at late growth stage. Meanwhile, the photosynthetic pigment contents and the net photosynthetic rate of peanut under single-seed sowing, especially in S₂ and S₃, were remarkably higher than those under traditional double-seed sowing. S₂ had the optimum population size with an equal distribution of individuals, which reduced the contradiction between individuals and population, optimized the canopy microenvironment, enhanced the photosynthetic characteristics, and increased the synthesis and accumulation of photosynthetic products to maximize the yield production of peanut.


Presence of Heat Shock mRNAs in Field Crown Soybeans.
Our laboratory has extensively defined many parameters of the heat shock (HS) response in etiolated soybean (Glycine max [L.] Merr.) hypocotyls, including the identification of cDNA clones for mRNAs encoding several low molecular weight HS proteins. We have now investigated the response of mature plants to a HS in a growth chamber and to high temperature stress under field conditions. Soybean plants show induction of HS mRNAs when the temperature of the chamber is rapidly shifted from 28 degrees C to 45 degrees C. This temperature of induction is significantly higher than the optimal induction temperature for etiolated hypocotyls, probably reflecting the ability of mature plants to lower their leaf temperatures below the ambient air temperature through transpirational cooling. Samples of soybean leaves were taken from an irrigated and a nonirrigated field during a 24-h period when midday temperatures reached 40 degrees C. Several HS mRNAs were present in samples from both fields, although the levels of these mRNAs were much higher in nonirrigated leaves. This differential response of HS mRNA steady state levels was not a response to water stress, since water-stressed plants at 28 degrees C did not induce HS mRNAS. Rather, these quantitative differences are probably due to differences in actual leaf temperatures between irrigated and nonirrigated leaves. The presence of these HS mRNAS in field-grown plants suggests that HS proteins are produced as part of the normal plant response to high temperature.


Synthesis of bandgap-controlled semiconducting single-walled carbon nanotubes.
Bandgap-controlled semiconducting single-walled carbon nanotubes (s-SWNTs) were synthesized using a uniquely designed catalytic layer (Al(2)O(3)/Fe/Al(2)O(3)) and conventional thermal chemical vapor deposition. Homogeneously sized Fe catalytic nanoparticles were prepared on the Al(2)O(3) layer and their sizes were controlled by simply modulating the annealing time via heat-driven diffusion and subsequent evaporation of Fe at 800 degrees C. Transmission electron microscopy and Raman spectroscopy revealed that the synthesized SWNTs diameter was manipulated from 1.4 to 0.8 nm with an extremely narrow diameter distribution below 0.1 nm as the annealing time is increased. As a result, the bandgap of semiconducting SWNTs was successfully controlled, ranging from 0.53 to 0.83 eV, with a sufficiently narrow energy distribution, which can be applied to field-effect transistors based on SWNTs.


Ischemia/reperfusion injury in rat mesenteric venules: red blood cell velocity and leukocyte rolling.
The authors determined the effects of 15 (n = 9) and 30 (n = 12) minutes of warm ischemia on the rat mesentery and compared the results with those of a sham-operated group (n = 10). Red blood cell velocity and number of rolling leukocytes were assessed before ischemia as well as 10, 20, 30, 60, 90, and 120 minutes after the start of reperfusion. Leukocyte rolling is considered to be an early step of the inflammatory process. Leukocytes roll along the vessel wall at a velocity that is clearly lower than that of the other blood cells. The preischemic values of red blood cell velocity and number of rolling leukocytes in the 15- and 30-minute ischemia groups did not differ from those of the sham group. In the sham group, no significant changes in red blood cell velocity and number of rolling leukocytes were observed over time. Compared with the sham group, the red blood cell velocity of the 15-minute ischemia group was significantly lower at 30, 60, 90, and 120 minutes after the start of reperfusion the number of rolling leukocytes did not differ significantly. For the 30-minute ischemia group, red blood cell velocity also was significantly lower at 20, 30, 60, 90, and 120 minutes after the start of reperfusion, and the number of rolling leukocytes was higher at 10, 20, and 30 minutes after the start of reperfusion. The results of this study indicate that short periods of total warm ischemia of the rat small bowel and subsequent reperfusion result in a significantly impaired microcirculatory blood flow in the mesentery. However, a prolonged period of ischemia is required to increase leukocyte-vessel wall interactions. In the future, this model will enable us to study the effect of pharmacological interventions during an early stage of the inflammatory response to ischemia/reperfusion in the gut.


Preexposure Prophylaxis Acceptability Among Pregnant Individuals and Implications for Human Immunodeficiency Virus Prevention.
To understand perspectives on and preferences for preexposure prophylaxis (PrEP) for pregnant individuals who are at risk for human immunodeficiency virus (HIV) infection. In this qualitative study, we purposively sampled and conducted in-depth interviews with pregnant participants at risk of HIV infection (indicated by a recent sexually transmitted infection [STI]) from a U.S. urban obstetrics clinic. Interview questions focused on perceived HIV risk, knowledge and perceptions of PrEP, and preferences for different PrEP formulations. We coded data using deductive and inductive codes, created matrices to explore patterns in findings, and wrote memos to interpret emergent themes. Twenty patients were enrolled. Median age of the participants was 24 years (interquartile range 19-26 years), 95.0% were African American, 65.0% were high school graduates, and 70.0% had unplanned pregnancies. Participants had low knowledge of PrEP and most saw themselves at low to no risk of HIV acquisition, despite their recent STI. Further, participants' low HIV risk perception and medication safety concerns reduced PrEP acceptability. Moreover, very few had discussed PrEP with their obstetrician-gynecologists (ob-gyns) during antenatal care, which further affected perceived acceptability. However, participants who did discuss PrEP with their ob-gyns had favorable perceptions of it. These participants indicated that they would choose a formulation based on individual preferences, which were largely shaped by perceived ease of use, acceptability, and prior experience with other medication regimens. Obstetrician-gynecologists may play an important role in increasing pregnant individuals' knowledge of and access to PrEP during pregnancy among those who are at risk of HIV acquisition. To maximize uptake and adherence during this time, PrEP formulations should be tailored to individual preferences. Prevention of HIV during this critical life transition is important not only for the long-term health and well-being of pregnant individuals and their infants, but to the plan to end the HIV epidemic in the United States by 2030.


Short-term supplementation of EPA-enriched ethanolamine plasmalogen increases the level of DHA in the brain and liver of n-3 PUFA deficient mice in early life after weaning.
A lack of n-3 polyunsaturated fatty acids (PUFAs) in mothers' diet significantly reduced the amount of docosahexaenoic acid (DHA) in the brains of offspring, which might affect their brain function. Our previous research has proven multiple benefits of eicosapentaenoic acid (EPA)-enriched ethanolamine plasmalogen (pPE) in enhancing the learning and memory ability. However, the effect of dietary supplementation with EPA-pPE on the DHA content in the brain and liver of offspring lacking n-3 PUFAs in early life is still unclear. Female ICR mice were fed with n-3 PUFA-deficient diets throughout the gestation and lactation periods to get n-3 PUFA-deficient offspring. The lipid profiles in the cerebral cortex and liver of offspring were analyzed using lipidomics after dietary supplementation with EPA-pPE (0.05%, w/w) and EPA-phosphatidylcholine (PC) (0.05%, w/w) for 2 weeks after weaning. Dietary supplementation with EPA could significantly change fatty acid composition in a variety of phospholipid molecular species compared with the n-3 deficient group. EPA-pPE and EPA-PC remarkably increased the DHA content in the brain PC, ether-linked phosphatidylcholine (ePC), and phosphatidylethanolamine plasmalogen (pPE) and liver triglyceride (TG), lyso-phosphatidylcholine (LPC), ePC, phosphatidylethanolamine (PE), and pPE molecular species, in which EPA-pPE showed more significant effects on the increase of DHA in cerebral cortex PC, ePC and liver PC compared with EPA-PC. Both EPA-phospholipids could effectively increase the DHA levels, and the pPE form was superior to PC in the contribution of DHA content in the cerebral cortex PC, ePC and liver PC molecular species. EPA-enriched ethanolamine plasmalogen might be a good nutritional supplement to increase DHA levels in the brains of n-3 PUFA-deficient offspring.


Effect of cetirizine on the inflammatory cells in mosquito bites.
Mosquito bites frequently cause wealing and delayed papules which appear within a few hours after the bites and may persist for several days. Cetirizine is an effective drug against mosquito bites by decreasing wealing and also the size and pruritus of the delayed bite papules. To characterize inflammatory cells in the delayed mosquito-bite lesions, and to study the effect of cetirizine on the inflammatory cell response. Twenty-six mosquito-bite sensitive subjects received cetirizine 20 mg (14 subjects) or placebo (12 subjects) in a double-blind fashion. Aedes aegypti-bites were given on a forearm and serial punch biopsies were taken at 2-, 6- and 24h after the bite exposure. Eosinophils, neutrophils, mast cells, mononuclear cells and T- helper (CD4+) and suppressor (CD8+) lymphocytes were counted from dermal infiltrates. Eosinophils and neutrophils were found already in 2-h bite lesions. Moreover, the number of mononuclear and CD4+ cells increased significantly (P < 0.01) from 2- to 24-h bite lesions. Unexpectedly, the overall numbers of eosinophils (P < 0.05), mononuclear cells (P < 0.01) and CD4+ cells (P < 0.01) were significantly higher in the cetirizine-treated subjects compared with the placebo-treated subjects. The results suggest that the inflammatory cell response in the delayed mosquito-bite lesions is similar to that occurring in allergic late-phase responses, i.e. an early influx of eosinophils, neutrophils and subsequent accumalation of CD4+ lymphocytes. The reason for the high numbers of eosinophils and CD4+ cells in the cetirizine-treated subjects is not known.


[15 years experience in the surgical treatment of decubitus ulcers of the pelvic region].
We summarize our 15 year experience in the surgical treatment of pressure ulcers of the pelvic region. The technique of suggested operations is described (sacral defect--gluteus maximus musculocutaneous V-Y advancement flap, trochanteric defect--tensor fascia lata musculofasciocutaneous transpositional flap, ischial defect--biceps femoris musculocutaneous V-Y advancement flap). In recent years we cover defects in all these regions using the principle of Emmett's hatchet flap--i.e. with musculocutaneous hatchet flap. We performed 105 operations, 3 patients had recurrence.


Serum amyloid A-to-albumin ratio as a potential biomarker to predict the activity, severity, and poor prognosis of systemic lupus erythematosus.
To evaluate the predictive value of serum amyloid A-to-albumin ratio (SAR) for active systemic lupus erythematosus (SLE), severe active SLE, and poor prognosis of SLE. One hundred and eighty-six patients with SLE undergoing treatment in our hospital were selected. The demographic characteristics, clinical data, and disease prognosis of all patients were collected and analyzed. There were significant differences in SLEDAI, total glyceride (TG), serum amyloid A (SAA), SAR, urinary microalbumin-to-creatinine ratio (ACR), erythrocyte sedimentation rate (ESR), albumin (ALB), complement 3 (C3), anti-dsDNA, anti-Sm positive rate, and anti-dsDNA positive rate between active SLE and stable SLE patients. TG, SAR, C3, ACR, and positive anti-dsDNA were independent influencing factors of active SLE, and the odds ratio (OR) values were 2.342, 10.921, 0.832, 1.451, and 2.476, respectively. The area under curves (AUCs) of SAA, ALB, and SAR for predicting active SLE and severe active SLE were 0.743, 0.724, 0.787, 0.711, 0.686, and 0.733, respectively. The AUC of SAR for predicting the poor prognosis of active SLE was 0.719. High SAR, high ACR, low C3, and positive anti-dsDNA were high risk factors for poor prognosis. Kaplan-Meier (K-M) survival analysis showed that patients with high SAR, high ACR, low C3, and positive anti-dsDNA had shorter continuous remission time than that with low SAR, low ACR, high C3, and negative anti-dsDNA. SAR had high predictive value for active SLE, severe active SLE, and poor prognosis of SLE. High SAR may be a potential marker for predicting the activity and prognosis of Chinese patients with SLE.


Lack of influence of pantoprazole on the disposition kinetics of theophylline in man.
The potential influence of pantoprazole (BY1023/SK&F96022), a newly developed selective inhibitor of the gastric H+,K(+)-ATPase, on therapeutic serum theophylline concentrations was investigated in a crossover study in 8 healthy male volunteers (age 25-30 [median 27] years, body weight 63-80 [median 68] kg). Steady-state serum theophylline concentrations were obtained by a two-step intravenous infusion scheme of approximately 350 mg theophylline each over 0.5 h and subsequently over approximately 10 h, respectively. In the test period, 30 mg pantoprazole were injected over 2 min on 5 consecutive days and theophylline was infused on day 4. In the reference period, placebo was administered i.v. on 2 consecutive days and theophylline on day 1. Serum pantoprazole concentrations were measured up to 12 h, serum theophylline concentrations up to 36 h. Pantoprazole was well tolerated with and without theophylline. There were no clinically relevant changes in blood pressure, heart rate, ECG and routine clinical laboratory parameters. Primary characteristic for confirmative assessment of no interaction was the area under the concentration/time curve (AUC). Lack of interaction in the sense of equivalence was concluded both for theophylline (with and without pantoprazole) and pantoprazole (with and without theophylline), as the 90%-confidence intervals of the AUC-ratio test/reference were within the equivalence range of 0.8 to 1.25. Further explorative analysis of theophylline disposition kinetics revealed this inclusion also for clearance and volume of distribution, but not for the half-life. In the case of pantoprazole, the corresponding 90%-confidence intervals for any of the secondary characteristics clearance, volume of distribution and half-life were within the above mentioned range. In conclusion, repeated once-daily i.v. injections of 30 mg pantoprazole have no clinically relevant influence on steady-state theophylline serum concentrations, nor does theophylline at therapeutic serum concentrations influence the pantoprazole disposition kinetics. Hence, in clinical practice theophylline and pantoprazole can be administered concomitantly without dose adjustment.


Functional roles of circular RNAs during epithelial-to-mesenchymal transition.
Cancer has become a major health issue worldwide, contributing to a high mortality rate. Tumor metastasis is attributed to the death of most patients. Epithelial-to-mesenchymal transition (EMT) plays a vital role in inducing metastasis. During EMT, epithelial cells lose their characteristics, such as cell-to-cell adhesion and cell polarity, and cells gain motility, migratory potential, and invasive properties to become mesenchymal stem cells. Circular RNAs (circRNAs) are closely associated with tumor metastasis and patient prognosis, as revealed by increasing lines of evidence. CircRNA is a type of single-stranded RNA that forms a covalently closed continuous loop. CircRNAs are insensitive to ribonucleases and are widespread in body fluids. This work is the first review on EMT-related circRNAs. In this review, we briefly discuss the characteristics and functions of circRNAs. The correlation of circRNAs with EMT has been reported, and we discuss the ways circRNAs can regulate EMT progression through EMT transcription factors, EMT-related signaling pathways, and other mechanisms. This work summarizes current studies on EMT-related circRNAs in various cancers and provides a theoretical basis for the use of EMT-related circRNAs in targeted management and therapy.


Species richness at the guild level: effects of species pool and local environmental conditions on stream macroinvertebrate communities.
1. A fundamental question in ecology is which factors determine species richness. Here, we studied the relative importance of regional species pool and local environmental characteristics in determining local species richness (LSR). Typically, this question has been studied using whole communities or a certain taxonomic group, although including species with widely varying biological traits in the same analysis may hinder the detection of ecologically meaningful patterns. 2. We studied the question above for whole stream macroinvertebrate community and within functional feeding guilds. We defined the local scale as a riffle site and the regional scale (i.e. representing the regional species pool) as a stream. Such intermediate-sized regional scale is rarely studied in this context. 3. We sampled altogether 100 sites, ten riffles (local scale) in each of ten streams (regional scale). We used the local-regional richness regression plots to study the overall effect of regional species pool on LSR. Variation partitioning was used to determine the relative importance of regional species pool and local environmental conditions for species richness. 4. The local-regional richness relationship was mainly linear, suggesting strong species pool effects. Only one guild showed some signs of curvilinearity. However, variation partitioning showed that local environmental characteristics accounted for a larger fraction of variance in LSR than regional species pool. Also, the relative importance of the fractions differed between the whole community and guilds, as well as among guilds. 5. This study indicates that the importance of the local and regional processes may vary depending on feeding guild and trophic level. We conclude that both the size of the regional species pool and local habitat characteristics are important in determining LSR of stream macroinvertebrates. Our results are in agreement with recent large-scale studies conducted in highly different study systems and complement the previous findings by showing that the interplay of regional and local factors is also important at intermediate regional scales.


[Membranoproliferative glomerulonephritis].
MPGN is characterized by its peculiar histological findings; lobular appearance, cellular and mesangial matrix proliferation and double contoured capillary loops. Based on histomorphalogical pattern, three types are subdivided. MPGN may be primary (in most children) or secondary (in most adults) to chronic infections, cryoglobulinemia or systemic autoimmune disorders. Clinical manifestation of typical MPGN is nephrotic range proteinuria associated with microscopic hematuria, showing slowly progressive course. Treatment strategy is composed of exclusion of pathogen, especially in HCV positive MPGN, and intervention to autoimmune mechanism such as alternative-day steroid regimen.


Seasonal affective disorder following brain injury.
Seasonal affective disorder has not previously been linked with neuroanatomical abnormalities despite its relationship to biological rhythms. A 45-year-old woman is described with an arteriovenous abnormality in the right frontotemporal region who developed recurrent winter depression and summer hypomania.


Adenosine-induced ST segment depression with normal perfusion.
Intravenous adenosine in conjunction with myocardial perfusion imaging is commonly used for the detection of coronary artery disease and risk assessment. We have previously shown that patients with ischemic changes on the 12-lead electrocardiogram (ECG) in response to adenosine but with normal perfusion pattern have a benign outcome on short intermediate follow-up. The long-term outcome of these patients is unknown. Patients with ischemic ECG response (> or = 1 mm ST depression) to adenosine infusion but with normal perfusion on single-photon emission computed tomography (SPECT) imaging in the absence of a history of myocardial infarction or coronary revascularization were followed up for mortality, myocardial infarctions, and coronary revascularization. The cohort consisted of 73 patients (81% women) who were followed up for mortality for a mean of 61 +/- 15 months. There were 10 deaths, and the cause of death was determined to be non-cardiac in half of those. Follow-up for the other endpoints was complete for 21 +/- 10 months during which no patient had myocardial infarction and seven underwent coronary revascularization. Patients with ischemic ECG response to intravenous adenosine administration and normal perfusion on SPECT are at low risk of cardiovascular events. The ST segment response to adenosine in this setting is likely related to non-ischemic mechanisms.


Osmoregulation and control of vasopressin secretion in healthy humans.
The functional characteristics of osmoregulated vasopressin secretion can be defined in terms of an osmotic threshold for its release and a sensitivity of the osmoreceptor and vasopressin-secreting unit. Osmotically stimulated thirst has features similar to osmoregulated vasopressin. There are wide individual variations in the functional characteristics of both thirst and vasopressin release in healthy humans, probably genetic in origin. The influence of aging appears to enhance the sensitivity of vasopressin secretion but blunt thirst appreciation. Yet in many physiological situations changes in osmoregulated vasopressin release and thirst occur in parallel. The fall in plasma osmolality associated with human pregnancy is accounted for entirely by a lowering of the osmotic thresholds for thirst and vasopressin release. Similar but less marked alterations accompany the ovulatory luteal phase of the menstrual cycle. A major nonosmotic stimulus to vasopressin secretion is hypotension and/or hypovolemia, mediated by high- (carotid sinus) and low- (left atrial) pressure receptors. Circulating catecholamines influence the release of vasopressin by alpha- and beta-adrenergic pathways. Drinking by hypertonic humans provides immediate reduction in thirst and vasopressin secretion probably mediated by pathways from the oropharynx. The modest but variable rise in plasma vasopressin in response to hypoglycemia appears to be due to cellular neuroglycopenia and is independent of parasympathetic pathways. Although osmotic and hemodynamic stimuli to vasopressin release do not act independently of each other, the precise subtle interactions between them and other nonosmotic stimuli remain to be clarified.


The effect of threat on novelty evoked amygdala responses.
A number of recent papers have suggested that the amygdala plays a role in the brain's novelty detection circuit. In a recent study, we showed that this role may be specific to certain classes of biologically-relevant stimuli, such as human faces. The purpose of the present experiment was to determine whether other biologically-relevant stimuli also evoke novelty specific amygdala responses. To test this idea, we presented novel and repeated images of snakes and flowers while measuring BOLD. Surprisingly, we found that novel images of snakes and flowers evoke more amygdala activity than repeated images of snakes and flowers. Our results further confirm the robustness of the novelty evoked amygdala responses, even when compared with effects more traditionally associated with the amygdala. In addition, our results suggest that threatening stimuli may prime the amygdala to respond to other types of stimuli as well.


Five cases of severe hyponatremia in the elderly successfully treated with low doses of hydrocortisone.
Hyponatremia is commonly defined as a serum sodium concentration of 135 mEq/L or less, which is reported to occur in 0.97-2.48% of hospitalized patients. Especially, in elderly patients, severe hyponatremia is sporadically developed without any complaints. Although a variety of causes of hyponatremia are documented, diagnosis of functional adrenal insufficiency is difficult because of a lack of the diagnostic criteria. In this case report, we present five cases of hyponatremia in the elderly, who were presumed to have functional adrenal insufficiency, successfully treated with low doses of hydrocortisone.


Distribution and appearance of elastic fibers in the dermis of clinically normal dogs and dogs with solar dermatitis and other dermatoses.
To determine the distribution and amount of elastic fibers in the dermis of clinically normal dogs and dogs with dermatoses, particularly solar dermatitis. Skin specimens from 7 anatomic sites were obtained from 19 clinically normal dogs after euthanasia to evaluate the normal distribution of elastic fibers. Biopsy specimens also were obtained from 34 dogs with dermatoses, including 16 with solar dermatitis. Tissue sections were stained with H&E, Verhoeff-van Gieson, and periodic acid-Schiff. 19 clinically normal dogs and 34 dogs with dermatoses. Numbers of elastic fibers were graded subjectively. Comparisons between clinically normal dogs and dogs with dermatoses were made. Normal elastic fibers were present in low numbers in the dermis of adult dogs, regardless of anatomic site or presence or severity of dermatitis. Condensed elastotic material was visualized in only 2 dogs with solar dermatitis. In both dogs, the elastotic material was Verhoeff-van Gieson and periodic acid-Schiff stain positive but was not visible with H&E stain. The most frequent histopathologic finding in the dermis of dogs with solar dermatitis was superficial dermal fibrosis. The dermis of clinically normal dogs does not contain abundant elastic fibers. Alterations of elastic fibers in dogs with solar dermatitis are rare. Superficial dermal fibrosis may be a better indicator of solar damage.


Human exposure to imidacloprid from dogs treated with advantage(r).
The objective of this investigation was twofold: (1) to determine the transferable residue of imidacloprid in gloves worn while petting experimental household dogs after the application of Advantage(R) and (2) to determine the imidacloprid residue in the dog's blood. Advantage(R) contains 9.1% imidacloprid, which controls fleas on dogs for up to 30 days. Imidacloprid produces toxicity by interacting with nicotinic receptors. Advantage(R) (364 mg imidacloprid/dog) was applied topically to six household dogs. The glove and blood samples were collected at 24 h, 72 h, and then on a weekly basis for 5 weeks post-Advantage(R) application. The glove samples were collected by petting each dog for 5 minutes while wearing a different glove per dog. The blood samples (5 mL from each dog) were collected into EDTA tubes. The imidacloprid residue was determined in the blood extracts and glove samples using RP-HPLC. The highest levels of imidacloprid residues were detected at the 24-h interval in both glove (254.16 +/- 25.49 ppm) and blood (54.06 +/- 3.00 ppb) samples. The blood imidacloprid residue was reduced by one third at the 72-h interval (18.73 +/- 2.00 ppb) and was not detected after 1 week. Imidacloprid residue in the glove samples decreased approximately one third between each collection interval. The residue of imidacloprid in the glove extract by the fourth week was very low (0.08 +/- 0.02 ppm) and not detected by the fifth week. The present findings suggest that following topical application of Advantage(R), imidacloprid residue can be detected in the dog's blood for up to 72 h, and transferable residue on the dog's coat can be detected for up to 4 weeks. Repeated chronic exposure to imidacloprid may pose possible health risks to veterinarians, veterinary technologists, dog caretakers, and owners.


Comparative study on the accelerative effect of "koushikon" and "nanshikon" and their constituents on proliferation of granuloma tissue in rats.
This study was carried out to compare the accelerative effect in ether extracts of "Koushikon" and "Nanshikon" on proliferation of granuloma tissue in rats, and to elucidate this effect on optical isomer of naphthoquinone derivatives in those extracts. The content of total naphthoquinone derivatives in the ether extracts of Koushikon and Nanshikon were found to be 56.1% and 25.4%. Among naphthoquinone derivatives, Koushikon contained mostly acetyl derivative and Nanshikon mostly teracryl derivative. The percentage of R-type (shikonin-type) in total naphthoquinone derivatives of the extracts was 85.5% and 3.8%. Each ether extract showed a dose-dependent acceleration on the cotton pellet-induced granuloma formation. Comparison with corresponding doses containing the same quantity of naphthoquinone derivatives showed the accelerative potency of ether extracts of Koushikon and Nanshikon to be about the same. The result suggests that the accelerative effect on proliferation of granuloma tissue depends primarily on the total content of naphthoquinone derivatives, and not on the ratio of the optically active isomers.


Time-dependent profiles of transcripts encoding lignocellulose-modifying enzymes of the white rot fungus Phanerochaete carnosa grown on multiple wood substrates.
The abundances of nine transcripts predicted to encode lignocellulose-modifying enzymes were measured over the course of Phanerochaete carnosa cultivation on four wood species. Profiles were consistent with sequential decay; transcripts encoding lignin-degrading peroxidases featured a significant substrate-dependent response. The chitin synthase gene was identified as the optimal internal reference gene for transcript quantification.


The baboon erythrocyte complement receptor is a glycophosphatidylinositol-linked protein encoded by a homologue of the human CR1-like genetic element.
The human erythrocyte CA receptor (E-CR) is the type 1 complement receptor (CR1), the most common form of which is a 220,000 Mr integral membrane glycoprotein composed of 30 short consensus repeats (SCRs). The E-CR of many nonhuman primates is a smaller receptor of unknown genetic origin. Recently, we identified a chimp cDNA, termed CR1b, which represented transcription of a homologue of the human genetic element, CR1-like. The purpose of this study was to identify CR1b in the baboon and, if present, determine whether it encodes the 65,000 Mr baboon E-CR. Baboon bone marrow cDNA was amplified by PCR using primers specific for the signal peptide-encoding region of human CR1 and the 3' region of chimp CR1b. This amplification yielded a CR1b sequence predicted to encode seven SCRs followed by a hydrophobic region, with an N terminus homologous to the N terminus of baboon E-CR. Expression of baboon CR1b yielded a membrane protein that reacted with an anti-CR1 mAb, was identical in size to baboon E-CR, and, like baboon E-CR, could bind baboon C3 linked to activated thiol-Sepharose (C3i-ATS), but not human C3i-ATS. Phosphatidylinositol-specific phospholipase C (PIPLC) released CR1b from Chinese hamster ovary cells and E-CR from baboon erythrocytes, demonstrating that both of these proteins are glycophosphatidylinositol linked to the membrane. Thus, the data indicate that baboon CR1b, a homologue of the human CR1-like genetic element, encodes a glycophosphatidylinositol-linked protein that is the baboon E-CR.


Thal Amyloid Stages Do Not Significantly Impact the Correlation Between Neuropathological Change and Cognition in the Alzheimer Disease Continuum.
The 2012 neuropathological criteria for the diagnosis of Alzheimer disease (AD) summarize the extent of AD neuropathological change with an ABC score, which is a composite of the Thal stage of amyloid deposition (A), the Braak stage of neurofibrillary tangles (NFTs) (B), and the CERAD neuritic plaque score (C). NFTs and neuritic plaques are well-established contributors to cognitive impairment, but whether the Thal amyloid stage independently predicts antemortem cognition remains unknown. We used the National Alzheimer's Coordinating Center autopsy data set to build adjacent-categories logit regression models with CDR-SOB and Mini-Mental State Examination (MMSE) scores as cognitive outcome variables. Increasing CERAD scores were independently associated with higher CDR-SOB scores, whereas increasing Braak NFT stages predicted both higher CDR-SOB and lower MMSE scores. Increasing Thal amyloid stages were not significantly independently associated with either outcome measure. Increasing ABC scores predicted higher CDR-SOB and lower MMSE scores. These results raise the possibility that Thal amyloid stages do not substantially contribute to predicting antemortem cognition compared to CERAD neuritic plaque scores and Braak NFT stages, and suggest that the diffuse amyloid deposits participating in the assignment of Thal amyloid stages are neutral with respect to clinically detectable cognitive and functional changes.


Bacteria Producing Extended Spectrum β-lactamases (ESBLs) in Hospitalized Patients: Prevalence, Antimicrobial Resistance Pattern and its Main Determinants.
There is a growing concern regarding the lack of new antibiotics, especially for multidrug- resistant bacteria that produce Extended Spectrum β-Lactamases (ESBLs). The present study aims to assess the preva- lence of bacteria producing ESBLs, their antimicrobial resistance pattern, and its main determinants among hospitalized patients. The study population included 383 consecutive patients with a definitive diagnosis of urinary tract infection (UTI). All eligible subjects for the study had a positive culture for gram-negative microorganisms in urine specimens. ESBL producing isolates were characterized phenotypically for ESBL production using the double disc synergy test. In total, 383 specimens were assessed, among which 212 (55.4%) were related to bacteria producing ESBLs (ESBL+). Of those with ESBL + infections, 65.5% were sourced from catheters (as hospital-associated UTIs), and 35.5% were categorized as community-associated UTIs. In the group consisting of bacteria producing ESBLs, the high- est sensitivity was observed with Imipenem (72.2%), while the highest resistance was revealed with ceftriaxone (100%). We have shown that our community faces a high prevalence of bacteria producing ESBLs, mostly sourced from the catheterization of hospitalized patients. The highest bacterial sensitivity was observed with Imipenem, nitrofu- rantoin, and amikacin, while the highest resistance was found with ceftriaxone and cotrimoxazole, suggesting the inef- fectiveness of using the two latter antibiotics for eradicating these bacterial infections. On the other hand, a history of urinary catheterization and previous hospitalization were two main determinants of their presence, a finding which em- phasizes the importance of avoiding catheterization and hospitalization of patients with UTIs without proper indications.


Review of regulations and guidelines for commercial and noncommercial drivers with sleep apnea and narcolepsy.
Studies show that persons with sleep disorders, such as sleep apnea and narcolepsy, have an increased incidence of automobile accidents. The goal of this study was to review any regulations or guidelines dealing with fitness to drive of persons with sleep disorders in all the 50 states and countries around the world. Several authorities in the United States and abroad in fact have produced guidelines or regulations stating that certain of these persons are not fit to drive. As of March 1994, only four states in the United States (Maryland, North Carolina, Oregon and Utah) had guidelines for narcolepsy, while two had guidelines for both narcolepsy and sleep apnea (California and Texas). In Maine, guidelines had been proposed for sleep apnea. In contrast, almost all Canadian provinces have guidelines for both sleep apnea and narcolepsy, as does the United Kingdom. There are, however, considerable variations in the nature of the regulations used in different states, Canadian provinces and countries. These variations are not based on scientific data. Currently the impact of these regulations on crash rates or on the practice of sleep medicine has not been assessed.


Individual differences in plasma ALT, AST and GGT: contributions of genetic and environmental factors, including alcohol consumption.
The causes of individuality of the plasma enzymes alanine aminotransferase (ALT; EC 220.127.116.11), aspartate aminotransferase (AST; EC 126.96.36.199) and gamma-glutamyl transferase (GGT; EC 188.8.131.52) were investigated in a study of 206 pairs of twins. Between-person variance was greater in men than women, while within-person variation was similar in both sexes. Plasma ALT and AST levels were affected by genetic factors, while GGT was affected by some environmental factor shared by co-twins. In the men, alcohol intake had a significant but small effect on all three enzyme levels, and since alcohol consumption was highly heritable, this appeared as a genetic influence on enzyme activities. The major factors involved in the observed correlations between these enzymes were a non-shared environmental factor other than alcohol affecting ALT, AST and GGT, and a genetic factor affecting only ALT and AST.


Factors Driving Bacterial Microbiota of Eggs from Commercial Hatcheries of European Seabass and Gilthead Seabream.
A comprehensive understanding of how bacterial community abundance changes in fishes during their lifecycle and the role of the microbiota on health and production is still lacking. From this perspective, the egg bacterial communities of two commercially farmed species, the European seabass (Dicentrarchus labrax) and the gilthead seabream (Sparus aurata), from different aquaculture sites were compared, and the potential effect of broodstock water microbiota and disinfectants on the egg microbiota was evaluated. Moreover, 16S ribosomal RNA gene sequencing was used to profile the bacterial communities of the eggs and broodstock water from three commercial hatcheries. Proteobacteria were the most common and dominant phyla across the samples (49.7% on average). Vibrio sp. was the most highly represented genus (7.1%), followed by Glaciecola (4.8%), Pseudoalteromonas (4.4%), and Colwellia (4.2%), in eggs and water across the sites. Routinely used iodine-based disinfectants slightly reduced the eggs' bacterial load but did not significantly change their composition. Site, species, and type of sample (eggs or water) drove the microbial community structure and influenced microbiome functional profiles. The egg and seawater microbiome composition differed in abundance but shared similar functional profiles. The strong impact of site and species on egg bacterial communities indicates that disease management needs to be site-specific and highlights the need for species- and site-specific optimization of disinfection protocols.


Patient with Phenylketonuria and Intellectual Disability-Problem Not Always Caused Exclusively by Insufficient Metabolic Control (Coexistence of PKU and Alazami Syndrome).
The authors present a case report of a boy with a classical form of phenylketonuria and Alazami syndrome. The inborn error of phenylalanine metabolism was diagnosed in the neonatal period based on population new-born screening. Despite early implementation of a low-phenylalanine diet and good biochemical control, the patient developed behavioural disorders and intellectual disability. He also presented with dysmorphic features. After long and extensive attempts to establish the genetic cause of this unusual phenotype, finally, at the age of 16 the boy was diagnosed with Alazami syndrome based on whole exome sequencing. The authors discussed the problem of neuropsychological disorders in patients with phenylketonuria and described typical clinical symptoms of Alazami syndrome. It was emphasized that the presence of one monogenic disease does not exclude the coexistence of another one.


Utility of Complete Mitochondrial Genomes in Phylogenetic Classification of the Species of Anopheles (Culicidae: Anophelinae).
Among the blood-sucking insects, Anopheles mosquitoes have a very special position, because they transmit parasites of the genus Plasmodium, which cause malaria as one of the main vector-borne disease worldwide. The aim of this review study was to evaluate utility of complete mitochondrial genomes in phylogenetic classification of the species of Anopheles. The complete mitochondrial genome sequences belonging to 28 species of the genus Anopheles (n=32) were downloaded from NCBI. The phylogenetic trees were constructed using the ML, NJ, ME, and Bayesian inference methods. In general, the results of the present survey revealed that the complete mitochondrial genomes act very accurately in recognition of the taxonomic and phylogenetic status of these species and provide a higher level of support than those based on individual or partial mitochondrial genes so that by using them, we can meticulously reconstruct and modify Anopheles classification. Understanding the taxonomic position of Anopheles, can be a very effective step in better planning for controlling these malaria vectors in the world and will improve our knowledge of their evolutionary biology.


Total sugar consumption and dental caries in Europe--an overview.
Sugar is the principal substrate for microorganisms causing dental caries. Positive correlations between caries prevalence and total sugar consumption in cross-sectional comparisons between different countries have been shown. This overview aims to relate caries prevalence at the age of 12 years to the total sugar consumption/person in 1970 and 1980 in European countries and also to give information about the trends in the two variables. Nationally representative oral health surveys have been quite rare and only a few studies on sugar consumption were identified. Nevertheless, there seemed to be a clear general trend of decreasing dental caries with only a minor decrease in total sugar consumption in the European countries studied.


Effect of prolonged low-dose methylprednisolone therapy in acute exacerbation of idiopathic pulmonary fibrosis.
We report on a 74-year-old man with an acute exacerbation of idiopathic pulmonary fibrosis (IPF) who was successfully treated with prolonged low-dose methylprednisolone, initiated at a loading dose of 2 mg/kg, followed by 2 mg/kg per day for 14 days. The dose was then tapered. The exacerbation observed on the chest radiograph and high-resolution computed tomography was found to have abated after the treatment. This successful case suggests the feasibility of this methylprednisolone treatment protocol for patients with IPF accompanied by accelerated deterioration. Furthermore, this case suggests possible similarities between acute exacerbation of IPF and late acute respiratory distress syndrome, as the same treatment protocol was previously proved to be beneficial for patients with late acute respiratory distress syndrome.


Improved recurrent neural network-based manipulator control with remote center of motion constraints: Experimental results.
In this paper, an improved recurrent neural network (RNN) scheme is proposed to perform the trajectory control of redundant robot manipulators using remote center of motion (RCM) constraints. Firstly, learning by demonstration is implemented to model the surgical operation skills in the Cartesian space. After that, considering the kinematic constraints associated with the optimization control of redundant manipulators, we propose a novel RNN-based approach to facilitate accurate task tracking based on the general quadratic performance index, which includes managing the constraints on RCM joint angle, and joint velocity, simultaneously. The results of the conducted theoretical analysis confirm that the RCM constraint has been established successfully, and accordingly. The corresponding end-effector tracking errors asymptotically converge to zero. Finally, demonstration experiments are conducted in a laboratory setup environment using KUKA LWR4+ to validate the effectiveness of the proposed control strategy.


Microdisplacement sensor using an optically trapped microprobe based on the interference scale.
Positioning technology is one of the most important technologies for developing microsystems. In particular, displacement sensors are necessary for positioning devices with nanoscale accuracy. In this study, we propose a new displacement sensor that uses an interference scale as a linear scale and a laser-trapped microsphere as a sensing probe. This sensor has a wide measuring range, high resolution, and accessibility for narrow target areas. A glass microsphere was optically trapped by means of the laser trapping technique. Between the target surface and the probe, an interference scale was generated along the optical axis. The scale origin was fixed on the target surface. The distance between the probe and the target surface could be measured in terms of the shift in the interference scale. This study investigated the fundamental performance of the sensor. The resolution and accuracy of the sensor were 10 and +/-50 nm, respectively; these values could be improved by using trapping lasers having shorter wavelengths. The measurable range was 250 microm. This sensor can provide useful displacement information from a target area having dimensions smaller than 15 microm. In addition, the displacement sensor can measure the distance even for surfaces inclined at angles less than 15 degrees; thus, a flexible arrangement can be used to carry out measurements. In addition, the direction of displacement can be identified.


The Escherichia coli retrons Ec67 and Ec86 replace DNA between the cos site and a transcription terminator of a 186-related prophage.
Retrons are unusual, reverse transcriptase-encoding elements found in bacteria. Although there are a number of indications that retrons are mobile elements, their transposition has not been observed. The Escherichia coli retrons Ec67 and Ec86 are different retrons inserted at the same site and we have further characterized this site in search of clues to the mechanism of retron transposition. We confirm, by extending previous sequence analysis, that Ec67 and Ec86 are inserted into prophages related to coliphage 186. Comparison with the recently published sequence of the 186 96-2% region indicates that the retrons have replaced approximately 180 bp of DNA between the phage cohesive end site (cos) and the transcription terminator of a phage DNA-packaging gene. These features--DNA replacement at the insertion site and the location of retron junctions near transcription terminators or DNA cleavage sites--are shared with other retrons and suggest ways in which retron transposition might have occurred.


Uterine leiomyomas in two Vietnamese pot-bellied pigs (Sus scrofa).
Two Vietnamese pot-bellied pigs (Sus scrofa) were euthanatized after they developed abdominal distension. Necropsy of both pigs revealed large myometrial neoplasms and cystic endometrial hyperplasia. Multiple discrete smaller myometrial neoplasms were also observed in one pig; however, distant metastases were not observed in either animal. The tumors were diagnosed as leiomyomas on the basis of histologic examination and immunohistochemistry. This is the first detailed report of uterine leiomyomas in swine, and it is suggested that this diagnosis may become more common as more aging pigs are examined.


Tonoplast targeting of VHA-a3 relies on a Rab5-mediated but Rab7-independent vacuolar trafficking route.
Vacuolar trafficking routes and their regulators have recently drawn lots of attention in plant cell biology. A recent study reported the discovery of a plant-specific vacuolar trafficking route, i.e., a direct ER-to-vacuole route, through analysis of VHA-a3 subcellular targeting, a key component for the tonoplast V-ATPases. Our recent findings showed that VHA-a3 targets to the tonoplast through a Rab5-mediated but Rab7-independent pathway, shedding new lights on the unconventional vacuolar trafficking route in plant cells.


Allee effects and conspecific cueing jointly lead to conspecific attraction.
Conspecific attraction is the preferential settlement into habitat patches with conspecifics. To be a good proximate strategy, fitness gains from settling with conspecifics must outweigh the costs of higher conspecific densities, such as intraspecific competition. Two types of benefits have been proposed to explain conspecific attraction: Allee effects (i.e., positive density dependence) and conspecific cueing (using conspecifics as an indicator of habitat quality). I present empirical evidence for conspecific attraction in the settlement of the porcelain crab, Petrolisthes cinctipes Randall (Anomura: Porcellanidae). Previous work demonstrated that P. cinctipes experiences strong intraspecific competition and that both Allee effects and conspecific cueing are present in P. cinctipes life-history. I developed an empirically-based fitness model of the costs and benefits of settling with conspecifics. Based on this model, I simulated optimal settlement to habitat patches that varied in conspecific density and habitat quality, where the correlation between density and habitat quality determined the level of conspecific cueing. I tested whether Allee effects alone, conspecific cueing alone, or Allee effects and conspecific cueing together could provide an ultimate explanation for the proximate settlement behavior of P. cinctipes. The settlement simulation was consistent with empirical settlement only when Allee effects and conspecific cueing were both included. Three life-history features are critical to this conclusion: (1) fitness is maximized at intermediate density, (2) fitness depends on the decisions of previous settlers, and (3) conspecific density provides good information about habitat quality. The quality of information garnered from conspecifics determines whether conspecific attraction is a good proximate strategy for settlement. I present a graphical illustration demonstrating how Allee effects and conspecific cueing work together to influence fitness, providing a conceptual framework for other systems.


Recent advances in the developmental origin of neuroblastoma: an overview.
Neuroblastoma (NB) is a pediatric tumor that originates from neural crest-derived cells undergoing a defective differentiation due to genomic and epigenetic impairments. Therefore, NB may arise at any final site reached by migrating neural crest cells (NCCs) and their progeny, preferentially in the adrenal medulla or in the para-spinal ganglia.NB shows a remarkable genetic heterogeneity including several chromosome/gene alterations and deregulated expression of key oncogenes that drive tumor initiation and promote disease progression.NB substantially contributes to childhood cancer mortality, with a survival rate of only 40% for high-risk patients suffering chemo-resistant relapse. Hence, NB remains a challenge in pediatric oncology and the need of designing new therapies targeted to specific genetic/epigenetic alterations become imperative to improve the outcome of high-risk NB patients with refractory disease or chemo-resistant relapse.In this review, we give a broad overview of the latest advances that have unraveled the developmental origin of NB and its complex epigenetic landscape.Single-cell RNA sequencing with spatial transcriptomics and lineage tracing have identified the NCC progeny involved in normal development and in NB oncogenesis, revealing that adrenal NB cells transcriptionally resemble immature neuroblasts or their closest progenitors. The comparison of adrenal NB cells from patients classified into risk subgroups with normal sympatho-adrenal cells has highlighted that tumor phenotype severity correlates with neuroblast differentiation grade.Transcriptional profiling of NB tumors has identified two cell identities that represent divergent differentiation states, i.e. undifferentiated mesenchymal (MES) and committed adrenergic (ADRN), able to interconvert by epigenetic reprogramming and to confer intra-tumoral heterogeneity and high plasticity to NB.Chromatin immunoprecipitation sequencing has disclosed the existence of two super-enhancers and their associated transcription factor networks underlying MES and ADRN identities and controlling NB gene expression programs.The discovery of NB-specific regulatory circuitries driving oncogenic transformation and maintaining the malignant state opens new perspectives on the design of innovative therapies targeted to the genetic and epigenetic determinants of NB. Remodeling the disrupted regulatory networks from a dysregulated expression, which blocks differentiation and enhances proliferation, toward a controlled expression that prompts the most differentiated state may represent a promising therapeutic strategy for NB.


Renal epithelioid angiomyolipoma: Histopathologic review, immunohistochemical evaluation and prognostic significance.
Epithelioid angiomyolipoma (EAML) is considered to be a potentially malignant tumor and requires a differential diagnosis from renal cell carcinoma. In this study, we assessed the clinicopathologic features of renal EAML and evaluated the prognostic significance. Among 78 angiomyolipoma (AML) patients, a total of 5 EAMLs were identified, accounting for 6.4% of the total AML cases. The mean age was 41.4 years, and the average tumor size was 12.7 cm in diameter. Association of tuberous sclerosis complex was identified in two cases. One EAML case showed malignant behavior with local recurrence and distant metastasis. The malignant EAML had a larger tumor size, a higher percentage of epithelioid component and atypical epithelioid cells, ≥2 mitoses per 10 high power fields with atypical mitosis, necrosis, extrarenal extension, and carcinoma-like growth pattern. Furthermore, the malignant case revealed p53 immunoreactivity and decreased membranous E-cadherin expression. Pathologic evaluation of adverse prognostic factors will be helpful for risk stratification and prognosis estimation of EAML patients.


Analysis of proteins from human breast epithelial cells using two-dimensional gel electrophoresis.
The human breast is a highly specialized, complex tissue comprised of a heterogeneous population of cells with varying functions. Interactions between the different cell types, changes in their relative abundance, state of differentiation and function in response to stimuli, as well as the alterations that lead to the aberrant growth associated with malignancy are poorly understood. Two-dimensional gel electrophoresis is being used to compare the proteins found in different breast cells in order to identify the gene products that are common or specific to particular cell types so as to provide markers that will be useful in studies of normal breast cell differentiation and the dedifferentiation or blocked differentiation characteristic of cancer. Protein patterns have been obtained from cells prepared for electrophoresis immediately after isolation from human milk, from cells cultured for fewer than ten passages after isolation from healthy breast tissue removed during reduction mammoplasty, and from cells maintained in long-term tissue culture after isolation from the pleural effusions of patients with breast carcinomas. Differential expression of cytokeratins 8, 18, and 19, shown previously to be predominantly expressed by epithelial cells in the luminal layer of breast tissue, was observed among the cells analyzed. Other non-cytokeratin proteins were also found to be differentially expressed in subsets of both the normal and tumor cells. A composite human breast cell protein pattern was created which includes all the commonly and specifically expressed proteins found in this study. This pattern will be the basis for continuing studies of proteins in the human breast.


Deficits in Social Behavior Precede Cognitive Decline in Middle-Aged Mice.
An extensive literature details deterioration of multiple brain functions, especially memory and learning, during aging in humans and in rodents. In contrast, the decline of social functions is less well understood. It is presently not clear whether age-dependent deficits observed in social behavior mainly reflect the disruption of social networks activity or are simply secondary to a more general impairment of cognitive and executive functions in older individuals. To address this issue, we carried out a battery of behavioral tasks exploring different brain functions in young (3 months) and middle-aged wild-type mice (9 months). Consistent with previous reports, our results show no obvious differences between these two groups in most of the domains investigated including learning and memory. Surprisingly, in social tasks, middle-aged animals showed significantly reduced levels of interactions when exposed to a new juvenile mouse. In the absence of overt cognitive decline, our findings suggest that social impairments may precede the disruption of other brain functions and argue for a selective vulnerability of social circuits during aging.


Cutaneous lymphomas: from morphology to chip technology.
Cutaneous lymphomas represent a heterogeneous group of malignant lymphoid diseases with particular tropism for the skin. Prognosis and treatment depend on the type of lymphoma, thus precise diagnosis and classification are of paramount importance. Classification of cutaneous lymphomas relies on a synthesis of all available information, including clinical history and presentation, histopathology, immunophenotype, and molecular data. Thanks to the efforts of the lymphoma groups of both the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC), a joint WHO-EORTC classification for primary cutaneous lymphomas has been proposed in 2005. The WHO-EORTC classification has been adsorbed with minor changes in the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues, thus including for the first time primary cutaneous lymphomas as distinct subtypes of extranodal lymphomas in a general classification of lymphomas.


Familial coaggregation of MASLD with hepatocellular carcinoma and adverse liver outcomes: Nationwide multigenerational cohort study.
Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is the fastest growing cause of hepatocellular carcinoma (HCC) worldwide. However, whether family members of individuals with MASLD also share an increased risk of developing HCC is unknown. This nationwide multigenerational cohort study involved family members of all Swedish adults diagnosed with biopsy-proven MASLD (1969-2017), and matched general population comparators. Using the Swedish Multi-generation Register, we identified 38,018 first-degree relatives (FDRs: parents, siblings, offspring) and 9,381 spouses of patients with MASLD, as well as 197,303 comparator FDRs and 47,572 comparator spouses. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) for HCC, major adverse liver outcomes (cirrhosis, decompensated liver disease or liver transplantation), liver-related mortality, extrahepatic cancer, and non-liver-related mortality. Over a median of 17.6 years, the rate of the primary outcome HCC was higher in MASLD FDRs vs. comparator FDRs (13 vs. 8/100,000 person-years [PY]; aHR 1.80, 95% CI 1.36-2.37). The HCC risk was further increased in FDRs of individuals with liver fibrosis/cirrhosis (aHR 2.14, 95% CI 1.07-4.27; PHeterogeneity = 0.03). MASLD FDRs also had higher rates of major adverse liver outcomes (73 vs. 51/100,000 PY; aHR 1.52, 95% CI 1.36-1.69) and liver-related mortality (20 vs. 11/100,000 PY; aHR 2.14, 95% CI 1.67-2.74). MASLD FDRs with any concomitant chronic liver condition experienced accelerated progression of liver disease (aHR 1.47, 95% CI 1.29-1.67). MASLD spouses were at higher risks of major adverse liver outcomes (86 vs. 74/100,000 PY; aHR 1.23, 95% CI 1.01-1.51) and liver-related mortality (25 vs. 19/100,000 PY; aHR 1.93, 95% CI 1.15-3.23), but not of HCC (aHR 1.43, 95% CI 0.87-2.35). There is distinct familial clustering of adverse liver-related outcomes in families of individuals with biopsy-proven MASLD, with higher relative risks of HCC, progressive liver disease, and liver-related mortality, but absolute risks are low. Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly termed NAFLD) clusters in families with high genetic susceptibility and shared environmental risk factors, but the risks of developing hepatocellular carcinoma and other major liver-related outcomes in family members of individuals with MASLD are largely unknown. This large nationwide multigenerational cohort study involving family members (first-degree relatives and spouses) of individuals with biopsy-proven MASLD and of matched general population comparators found slightly increased risks of hepatocellular carcinoma in first-degree relatives, and of developing cirrhosis and liver-related mortality in all family members of individuals with biopsy-proven MASLD. The findings of this study provide large-scale evidence to inform clinical practice guidelines for recommendations on the early identification of individuals at higher risk of liver-related morbidity and mortality.


4-1BB-mediated expansion affords superior detection of in vivo primed effector memory CD8+ T cells from melanoma sentinel lymph nodes.
We have been studying the re-activation of tumor-associated antigen (TAA)-specific CD8(+) T cells in sentinel lymph nodes (SLN) of melanoma patients upon intradermal administration of the CpG-B oligodeoxynucleotide PF-3512676. To facilitate functional testing of T cells from small SLN samples, high-efficiency polyclonal T cell expansion is required. In this study, SLN cells were expanded via classic methodologies with plate- or bead-bound anti-CD3/CD28 antibodies and with the K562/CD32/4-1BBL artificial APC system (K32/4-1BBL aAPC) and analyzed for responsiveness to common recall or TAA-derived peptides. K32/4-1BBL-expanded T cell populations contained significantly more effector/memory CD8(+) T cells. Moreover, recall and melanoma antigen-specific CD8(+) T cells were more frequently detected in K32/4-1BBL-expanded samples as compared with anti-CD3/CD28-expanded samples. We conclude that K32/4-1BBL aAPC are superior to anti-CD3/CD28 antibodies for the expansion of in vivo-primed specific CD8(+) T cells and that their use facilitates the sensitive monitoring of functional anti-tumor T cell immunity in SLN.


Thermoelectrochemical Seebeck coefficient and viscosity of Co-complex electrolytes rationalized by the Einstein relation, Jones-Dole B coefficient, and quantum-chemical calculations.
The Seebeck coefficient (Se) and the viscosity of a redox electrolyte are the key characteristics of thermoelectrochemical cells that generate electric power from waste thermal energy. However, the recent upsurge of research in this field is seriously disconnected from the knowledge of solution chemistry explored in the previous century. Herein, we systematically investigate five redox couples of cobalt complexes containing different aromatic ligands and anions in γ-butyrolactone solvent to demonstrate how the Einstein relation of hydrodynamic theory and the Jones-Dole B coefficient obtained from viscosity measurements can be used to account for such electrolyte properties. In essence, we reveal that the outer-shell (solvent reorganization) and inner-shell (metal-ligand reorganization) contributions to the redox reaction entropy ΔSrc (∝Se) can be quantified by the analyses using the B-coefficients and quantum-chemical simulations, respectively, while the distinct regimes found in the viscosity and conductivity are well accounted for by the Einstein relation, despite its classical hydrodynamic origin.


Application of a shape-memory alloy internal fixator for treatment of acetabular fractures with a follow-up of two to nine years in China.
Displaced acetabular fractures should be treated surgically. Over the past decade, surgical approaches to the acetabulum and the surgical technique for repair of common fracture patterns have advanced. Excellent outcomes after repair of these injuries can be achieved. The aim of this study was to assess the medium-term results of reconstruction of acetabular fractures by using shape-memory alloy designed by the authors. This is a retrospective review conducted at a level 1 trauma centre. From October 1999 to July 2009, 19 patients with acetabular fractures were treated with our patented Ni-Ti shape-memory alloy acetabular tridimensional memory alloy-fixation system (ATMFS). The ATMFS device was cooled with ice before implantation and then warmed to 40-50°C after implantation to produce balanced axial and compression forces that would stabilise the fracture three dimensionally. Our results are as follows; according to the D'Aubigne-Postel scoring system: Fifteen cases out of 19 (79%) achieved excellent or good clinical results. In two patients, late complications included avascular necrosis of the femoral head (ANFH) associated with posterior dislocation of the hip joint two years after the operation. We also observed two cases of grade II or III ectopic ossification, with good hip function, and one case of traumatic arthritis. In conclusion, these results demonstrate the effectiveness of the ATMFS device for the management of acetabular fracture. The device provides continuous compression of the fracture with minimal disruption to the local blood supply.


Managing anemia in low-income toddlers: barriers, challenges and context in primary care.
Iron-deficiency remains a concern among low-income toddlers in the U.S. This formative study describes how primary care providers serving high-risk 1- to 3-year-old children in an urban ambulatory care setting approach anemia. Data collection included a retrospective review of randomly selected medical records (n=264) and semi-structured interviews with clinicians (n=41). Thirty-eight percent of the children presented with anemia (Hgb < 11.0 g/dl) at least once between 12 and 36 months of age. Just under half of these children were treated for anemia. Follow-up laboratories for iron-treated children were completed within 35 days in 16% of cases (median: 3 months). Interviews identified four key themes (iron-deficiency, communication, poverty, system) running through the two major categories of prevention and treatment. Treatment cut-points were variable. While providers felt clinically comfortable with anemia, they felt burdened and challenged by follow-up. Communication and system barriers weighed most heavily on perceived treatment outcomes.


Percutaneous/minimally invasive techniques in treatment of femoral shaft fractures with an intramedullary nail.
Intramedullary nailing of the femur is often the treatment of choice in isolated fractures of the femoral shaft. Some surgeons are reticent to use intramedullary nailing for proximal and distal femoral fractures. However, indications for femoral nailing can be appropriately extended to highly comminuted fractures as well as distal and proximal fractures when the correct technique and reduction maneuvers are utilized. Implementation of these techniques will also respect the critical soft tissue envelope that is so important in fracture healing. Deforming forces of the muscles of the hip, knee and thigh are neutralized with reduction tools applied percutaneously, blocking screws and Schanz pins. Mastery of these techniques and appropriate reduction are incumbent on the orthopaedic surgeon treating femoral shaft fractures.


Ambient condition desensitization of a fiber Raman temperature sensing system based on a dynamic sampling-correction scheme.
One of the most important performance indicators of a fiber optic distributed temperature sensing (DTS) system is its operational stability, which depends on the performance of each device making up the system. Such individual device performance itself is affected by temperature and other environmental conditions. As a result, ambient fluctuations invariably lead to measurement uncertainties and drifts, seriously degrading the system performance. To ameliorate such adverse effects of the environment, we propose a dynamic sampling-correction scheme, which we have implemented on our fiber optic Raman DTS system, resulting in an average temperature error within 1°C when the main chassis undergoes a temperature variation over the range -25°C-45°C. The drastically improved system stability foreshadows better performance and reliability in engineering applications.


Serum insulin-like growth factor-I concentrations in the recovery of patients with anorexia nervosa.
Anorexia nervosa (AN) can result in extreme malnutrition, and these patients frequently require inordinately large amounts of calories to gain weight during refeeding therapy. Insulin-like growth factor-I (IGF-I) is a polypeptide that mediates many of the anabolic effects of growth hormone. Low levels of IGF-I have been associated with malnutrition and can cause poor weight gain. To clarify the potential relationship of IGF-I to weight gain, serial serum IGF-I, retinol-binding protein and prealbumin levels were measured at admission, 2 weeks and 4 weeks, in 14 consecutive consenting patients admitted for treatment of AN. Baseline IGF-I levels were lower in the patients compared to age-matched controls (mean 20.8 +/- 2.5 vs 32.9 +/- 2.9 nmol/L, p < 0.01). In patients with no weight gain, IGF-I levels were static. There was a stepwise increment in the IGF-I values related to weight gain. Retinol-binding protein and prealbumin, proteins commonly used to assess nutritional status, did not demonstrate important correlations with weight gain. Further studies are required to determine whether or not initial low IGF-I levels impede weight gain in AN patients and whether treatment with IGF-I (possibly in combination with growth hormone) may be of benefit in this disease process.


Stable GeV ion-beam acceleration from thin foils by circularly polarized laser pulses.
A stable relativistic ion acceleration regime for thin foils irradiated by circularly polarized laser pulses is suggested. In this regime, the "light-sail" stage of radiation pressure acceleration for ions is smoothly connected with the initial relativistic "hole-boring" stage, and a defined relationship between laser intensity I0, foil density n{0}, and thickness l{0} should be satisfied. For foils with a wide range of n{0}, the required I0 and l{0} for the regime are theoretically estimated and verified with the particle-in-cell code ILLUMINATION. It is shown for the first time by 2D simulations that high-density monoenergetic ion beams with energy above GeV/u and divergence of 10 degrees are produced by circularly polarized lasers at intensities of 10;{22} W/cm;{2}, which are within reach of current laser systems.


Best practice in caring for adults with dementia and learning disabilities.
People with learning disabilities, particularly Down's syndrome, are at increased risk of dementia. At present, services and care tailored to people with both dementia and a learning disability are unsatisfactory. This article reviews the literature specific to dementia in people with learning disabilities, including: comprehensive screening, diagnosis, management, environmental considerations, end of life care and training issues for nursing staff. Recommendations for best practice and service improvement are made to improve the quality of life for individuals with dementia and learning disabilities, pre and post-diagnosis.


Habits of nervous tension and suicide.
In a prospective study of 1,046 male medical students, those who later committed suicide showed a heightened sensitivity in stressful situations as assessed by the Habits of Nervous Tension Questionnaire (HNT). Survival analyses specified 2 of the 25 HNT items as the strongest suicide predictors: Irritability (relative risk 5.5; 95% confidence interval 1.76-17.17) and Urinary Frequency (3.3; 1.07-10.32). No other risk factors for suicide emerged from family background measures or individual medical school measures. It appears that types of sensitivity reflect psychological characteristics that are long-term precursors of suicide.


Antibiogram Screening and Detection of Virulence-Associated Genes in Brucella Species Acquired from Cattle in South Africa's Eastern Cape Province.
Brucellosis is a widespread zoonotic illness, and it poses serious public health and economic risks. The purpose of this investigation is to look at the antimicrobial susceptibility of unpasteurized milk, blood, and lymph node specimens from cattle, goats, and sheep, as well as to identify virulence-associated genes. In this investigation, a total of 123 isolates were examined. The activity of 15 antimicrobials against Brucella pathogens were assessed using the Kirby−Bauer disk diffusion technique. Nine virulence factors were detected with polymerase chain reaction analysis. Five antibiotics were 100% effective against Brucella isolates. A high level of resistance (100%) was documented with streptomycin, penicillin, and seven more antibiotics. Doxycycline resistance was found in 12% of goat isolates, and tetracycline resistance was found in 21% and 44% of goat and sheep isolates, respectively. Multiple antibiotic resistance (MAR) index >0.2 was found in 38.2% (47/123) of Brucella isolates. VecC and BetB, two B. abortus genes, were confirmed to be comparable. The findings of this study suggests that Brucella spp. are reservoirs of antibiotic resistance in the Eastern Cape Province. As such, they represent a potential pool of antibiotic genes that might be transferred to other pathogens in the community, and thus continue to pose a healthcare hazard.


Successful treatment of post-cholecystectomy bile leaks using nasobiliary tube drainage and sphincterotomy.
Bile leaks are known complications of cholecystectomy. The combination of sphincterotomy and nasobiliary tube (NBT) drainage is effective for the immediate decompression of bile ducts and provides access for follow-up cholangiography. Our objective was to study, retrospectively, 19 patients who had undergone treatment for bile leaks with this combination between October 1991 and December 1995. Nineteen patients (15 F, 4 M) ages 23-83 yr (mean 50 yr) presented with bile leaks secondary to open cholecystectomy (n = 1) and laparoscopic cholecystectomy (n = 18). All patients had sphincterotomy and NBT placement. Symptoms, findings at ERCP, and outcome were reviewed. Patients presented from 0 to 150 days after cholecystectomy (median = 2) with pain (n = 17), fever (n = 8), bile leakage in a surgical drain (n = 4), elevated liver tests (n = 8), and nausea and vomiting (n = 4). Fourteen patients had diagnostic imaging before endoscopic management. ERCP findings included cystic stump leak (n = 12), including one with a colocutaneous biliary fistula, gallbladder fossa leak (n = 3), right hepatic branch leak (n = 1), or no leak (n = 3). Three patients had choledocholithiasis. NBT drainage was used for a mean of 3.9 days (range 1-12 days). Fourteen patients had radiographic evidence of leak closure. One patient ultimately required surgical correction for a chronic colocutaneous biliary fistula. There were no early or late endoscopic complications. Endoscopic management with nasobiliary drainage and sphincterotomy is effective for acute uncomplicated bile leaks but may not be adequate for chronic fistulas. The advantages over endoprostheses include access for subsequent cholangiography, improved biliary decompression, and catheter removal without further endoscopy.


In situ mRNA hybridization technique for analysis of metastasis-related genes in human colon carcinoma cells.
The purpose of this study was to determine whether the expression level of several genes that regulate different steps of the metastatic process correlates with the metastatic potential of human colon carcinoma cells. The mRNA expression level for epidermal growth factor receptor (growth), basic fibroblast growth factor and interleukin-8 (angiogenesis), type IV collagenase (invasion), E-cadherin and carcinoembryonic antigen (adhesion), and the multidrug resistance gene mdr-1 (drug resistance) in the human KM12 colon carcinoma cell lines and clones with different metastatic potential was measured by Northern blot analysis and by in situ hybridization technique. Highly metastatic KM12SM and KM1214 cells growing in culture uniformly expressed high levels of epidermal growth factor receptor, basic fibroblast growth factor, and carcinoembryonic antigen mRNA, whereas cultures of low metastatic KM12C, clone 1, clone 3, and clone 6 cells displayed heterogeneous patterns of expression. KM12C (low metastatic) and KM12SM (highly metastatic) cells were implanted into the subcutis (ectopic) or the wall of the cecum (orthotopic) of nude mice. The mRNA expression level for epidermal growth factor receptor, basic fibroblast growth factor, interleukin-8, type IV collagenase, carcinoembryonic antigen, and mdr-1 was increased in the cecal wall tumors as compared with subcutaneous tumors or in vitro cultures. These data demonstrate a direct correlation between constitutive and inducible expression of several metastasis-related genes and the metastatic potential of human colon carcinoma cells.


[Resection of pancreatic cancer and simultaneous lung metastasis--a case report of successful in tumor dormancy mainly by postoperative 5-fluorouracil-based chemotherapy].
A 48-year-old male patient was admitted to our institution with left hypochondralgia. Preoperative serum CEA was 504 ng/ml. Under a radiological diagnosis of simultaneous double cancer of the pancreas and lung, resection was performed. Pathological study revealed primary pancreatic cancer with lung metastasis. After the operation, serum CEA fell to 55 ng/ml. Seventeen months later, bowel obstruction occurred and serum CEA was 140 ng/ml. One course of systemic chemotherapy, using the combination of CDDP, 5-FU and Leucovorin, was successful. After another three months, however, the same clinical symptoms occurred. With no response to the prior chemotherapy regimen, surgery was undertaken and a mass at the mesentery was removed. Fifty-nine months have passed since the initial operation and the patient is free of disease, though his serum CEA is around 50 ng/ml. In conclusion, there are cases of pancreatic cancer in which tumor dormancy can be achieved by postoperative 5-FU based chemotherapy.


The influence of abdominal pigmentation on desiccation and ultraviolet resistance in two species of Drosophila.
Drosophila yakuba and D. santomea are sister species that differ in their levels of abdominal pigmentation; D. yakuba shows heavily pigmented posterior abdominal segments in both sexes, whereas D. santomea lacks dark pigment anywhere on its body. Using naturally collected lines, we demonstrate the existence of altitudinal variation in abdominal pigmentation in D. yakuba but not in D. santomea. We use the variation in pigmentation within D. yakuba and two body-color mutants in D. yakuba to elucidate selective advantage of differences in pigmentation. Our results indicate that although differences in abdominal pigmentation have no effect on desiccation resistance, lighter pigmentation confers ultraviolet radiation resistance in this pair of species.


Microtubule assembly in growing dendrites.
Dendritic microtubules (MTs) are nonuniform with respect to polarity orientation, with roughly equal proportions having a plus-end-distal or minus-end-distal orientation. In the present studies, we have microinjected biotin-labeled tubulin (Bt-tub) into cultured sympathetic neurons extending dendrites to explore the contribution of MT assembly to the elaboration and maintenance of the dendritic MT array. Within minutes of injecting Bt-tub, an enormous number of MTs were seen emanating from a point source in the cell body. Over time, this pattern changed such that by 120 min after injection, biotinylated MTs no longer emanated from a discrete site, but were distributed over a broad region that extended from the cell body into the dendrites. The observation that biotinylated MTs emanate from a point source in the soma at relatively short times after injection, but not at longer times, suggests that they undergo a redistribution subsequent to their initial nucleation rather than a simple radial expansion from the somal nucleation site. Bt-tub assembly also occurred in dendrites but, unlike in the cell body, assembly was dispersed throughout the dendrite rather than emanating from a discrete site. Immunoelectron microscopic analyses revealed that assembly in dendrites reflected the addition of Bt-tub onto the ends of both plus-end-distal and minus-end-distal MTs that existed in the cell at the time of injection. The time course of Bt-tub appearance in dendritic MTs suggested an average half-life of approximately 76 min for these MTs. We discuss these observations in the context of a model for generating the MT array of dendrites that combines both MT transport and MT assembly.


Optogenetic control of cellular forces and mechanotransduction.
Contractile forces are the end effectors of cell migration, division, morphogenesis, wound healing and cancer invasion. Here we report optogenetic tools to upregulate and downregulate such forces with high spatiotemporal accuracy. The technology relies on controlling the subcellular activation of RhoA using the CRY2/CIBN light-gated dimerizer system. We fused the catalytic domain (DHPH domain) of the RhoA activator ARHGEF11 to CRY2-mCherry (optoGEF-RhoA) and engineered its binding partner CIBN to bind either to the plasma membrane or to the mitochondrial membrane. Translocation of optoGEF-RhoA to the plasma membrane causes a rapid and local increase in cellular traction, intercellular tension and tissue compaction. By contrast, translocation of optoGEF-RhoA to mitochondria results in opposite changes in these physical properties. Cellular changes in contractility are paralleled by modifications in the nuclear localization of the transcriptional regulator YAP, thus showing the ability of our approach to control mechanotransductory signalling pathways in time and space.


'Inductive' charges on atoms in proteins: comparative docking with the extended steroid benchmark set and discovery of a novel SHBG ligand.
We have developed a novel iterative approach for calculation of partial charges in proteins within the framework of the 'molecular capacitance' model. The method operates by an effective 'inductive' electronegativity scale derived from a number of the conventional charge systems including CHARMM, AMBER, MMFF, OPLS, and PEOE among others. Our novel 'inductive' electronegativity equalization procedure allows rapid and conformation sensitive computation of adequate partial charges in proteins. Accuracy of the 'inductive' values was confirmed by their correlation with DFT-computed partial charges in common amino acids. A comparative docking study with an extended steroid data set not only illustrated the adequacy of 'inductive' protein charges but also demonstrated their superior performance compared to several conventional protein charging systems. Subsequent docking with 'inductive' charges resulted in identification of five potential leads as human Sex Hormone Binding Globulin (SHBG) ligands from a commercial library of natural compounds. When the selected substances were evaluated for their ability to bind SHBG in vitro, three of them displaced testosterone from the SHBG steroid-binding site, and with one compound this was achieved at micromolar concentrations.


Self-assembled nitride-metal nanocomposites: recent progress and future prospects.
Two-phase nanocomposites have gained significant research interest because of their multifunctionalities, tunable geometries and potential device applications. Different from the previously demonstrated oxide-oxide 2-phase nanocomposites, coupling nitrides with metals shows high potential for building alternative hybrid plasmonic metamaterials towards chemical sensing, tunable plasmonics, and nonlinear optics. Unique advantages, including distinct atomic interface, excellent crystalline quality, large-scale surface coverage and durable solid-state platform, address the high demand for new hybrid metamaterial designs for versatile optical material needs. This review summarizes the recent progress on nitride-metal nanocomposites, specifically targeting bottom-up self-assembled nanocomposite thin films. Various morphologies including vertically aligned nanocomposites (VANs), self-organized nanoinclusions, and nanoholes fabricated by additional chemical treatments are introduced. Starting from thin film nucleation and growth, the prerequisites of successful strain coupling and the underlying growth mechanisms are discussed. These findings facilitate a better control of tunable nanostructures and optical functionalities. Future research directions are proposed, including morphological control of the secondary phase to enhance its homogeneity, coupling nitrides with magnetic phase for the magneto-optical effect and growing all-ceramic nanocomposites to extend functionalities and anisotropy.


"My World is Upside Down": Transnational Iraqi Youth and Parent Perspectives on Resettlement in the United States.
The U.S. war with Iraq led to the displacement of millions of Iraqis, many of whom have resettled in the United States as refugees. We explore the challenges Iraqi families face after resettlement, with a particular focus on the agency of refugees and challenges/opportunities of familial social reproduction in a transnational context. We conducted 181 qualitative interviews with 38 Iraqis (11 youth, 27 adults) and 5 service providers. Our findings highlight the importance of exploring refugee agency and illuminate how the interplay between structure and agency in transnational contexts is a useful framework for understanding transformations around social roles.


Characterization of photosystem II assembly complexes containing ONE-HELIX PROTEIN1 in Arabidopsis thaliana.
The assembly process of photosystem II (PSII) requires several auxiliary proteins to form assembly intermediates. In plants, early assembly intermediates comprise D1 and D2 subunits of PSII together with a few auxiliary proteins including at least ONE-HELIX PROTEIN1 (OHP1), OHP2, and HIGH-CHLOROPHYLL FLUORESCENCE 244 (HCF244) proteins. Herein, we report the basic characterization of the assembling intermediates, which we purified from Arabidopsis transgenic plants overexpressing a tagged OHP1 protein and named the OHP1 complexes. We analyzed two major forms of OHP1 complexes by mass spectrometry, which revealed that the complexes consist of OHP1, OHP2, and HCF244 in addition to the PSII subunits D1, D2, and cytochrome b559. Analysis of chlorophyll fluorescence showed that a major form of the complex binds chlorophyll a and carotenoids and performs quenching with a time constant of 420 ps. To identify the localization of the auxiliary proteins, we solubilized thylakoid membranes using a digitonin derivative, glycodiosgenin, and separated them into three fractions by ultracentrifugation, and detected these proteins in the loose pellet containing the stroma lamellae and the grana margins together with two chlorophyll biosynthesis enzymes. The results indicated that chlorophyll biosynthesis and assembly may take place in the same compartments of thylakoid membranes. Inducible suppression of the OHP2 mRNA substantially decreased the OHP2 protein in mature Arabidopsis leaves without a significant reduction in the maximum quantum yield of PSII under low-light conditions, but it compromised the yields under high-light conditions. This implies that the auxiliary protein is required for acclimation to high-light conditions.


Structural Insights into How Protein Environments Tune the Spectroscopic Properties of a Noncanonical Amino Acid Fluorophore.
Genetically encoded fluorescent noncanonical amino acids (fNCAAs) could be used to develop novel fluorescent sensors of protein function. Previous efforts toward this goal have been limited by the lack of extensive physicochemical and structural characterizations of protein-based sensors containing fNCAAs. Here, we report the steady-state spectroscopic properties and first structural analyses of an fNCAA-containing Fab fragment of the 5c8 antibody, which binds human CD40L. A previously reported 5c8 variant in which the light chain residue IleL98 is replaced with the fNCAA l-(7-hydroxycoumarin-4-yl)ethylglycine (7-HCAA) exhibits a 1.7-fold increase in fluorescence upon antigen binding. Determination and comparison of the apparent pKas of 7-HCAA in the unbound and bound forms indicate that the observed increase in fluorescence is not the result of perturbations in pKa. Crystal structures of the fNCAA-containing Fab in the apo and bound forms reveal interactions between the 7-HCAA side chain and surrounding residues that are disrupted upon antigen binding. This structural characterization not only provides insight into the manner in which protein environments can modulate the fluorescence properties of 7-HCAA but also could serve as a starting point for the rational design of new fluorescent protein-based reporters of protein function.


RiPerC Attenuates Cerebral Ischemia Injury through Regulation of miR-98/PIK3IP1/PI3K/AKT Signaling Pathway.
Cerebral ischemic stroke is a refractory disease which seriously endangers human health. Remote ischemic perconditioning (RiPerC) by which the sublethal ischemic stimulus is administered during the ischemic event is beneficial after an acute stroke. However, the regulatory mechanism of RiPerC that relieves cerebral ischemic injury is still not completely clear. In the present study, we investigated the regulatory mechanism of RiPerC in a rat model of ischemia induced by the middle cerebral artery occlusion (MCAO). Forty-eight adult male Sprague-Dawley (SD) rats were injected intracerebroventricularly with miR-98 agomir, miR-98 antagomir, or their negative controls (agomir-NC, antagomir-NC) 2 h before MCAO or MCAO+RiPerC followed by animal behavior tests and infraction volume measurement at 24 h after MCAO. The expression of miR-98, PIK3IP1, and tight junction proteins in rat hippocampus and cerebral cortex tissues was detected by quantitative polymerase chain reaction (qPCR) and Western blot (WB). Enzyme-linked immunosorbent assay (ELISA) was used to assess the IL-1β, IL-6, and TNF-α levels in the rat serum. The results showed that in MCAO group, the expression of PIK3IP1 was upregulated, but decreased after RiPerC treatment. Then, we found that PIK3IP1 was a potential target of miR-98. Treatment with miR-98 agomir decreased the infraction volume, reduced brain edema, and improved neurological functions compared to control rats. But treating with miR-98 antagomir in RiPerC group, the protective effect on cerebral ischemia injury was canceled. Our finding indicated that RiPerC inhibited the MCAO-induced expression of PIK3IP1 through upregulated miR-98, thereby reducing the apoptosis induced by PIK3IP1 through the PI3K/AKT signaling pathway, thus reducing the cerebral ischemia-reperfusion injury.


Characterization of ADAT2/3 molecules in Trypanosoma cruzi and regulation of mucin gene expression by tRNA editing.
Adenosine-to-inosine conversion at position 34 (A34-to-I) of certain tRNAs is essential for expanding their decoding capacity. This reaction is catalyzed by the adenosine deaminase acting on tRNA (ADAT) complex, which in Eukarya is formed by two subunits: ADAT2 and ADAT3. We herein identified and thoroughly characterized the ADAT molecules from the protozoan pathogen Trypanosoma cruzi, the causative agent of Chagas Disease. TcADAT2 and TcADAT3 spontaneously form a catalytically active complex, as shown by expression in engineered bacteria and/or by the increased ex vivo tRNA A-to-I deamination activity of T. cruzi epimastigotes overexpressing TcADAT subunits. Importantly, enhanced TcADAT2/3 activity in transgenic parasites caused a shift in their in vivo tRNAThrAGU signature, which correlated with significant changes in the expression of the Thr-rich TcSMUG proteins. To our knowledge, this is the first evidence indicating that T. cruzi tRNA editing can be modulated in vivo, in turn post-transcriptionally changing the expression of specific genes. Our findings suggest tRNA editing/availability as a forcible step in controlling gene expression and driving codon adaptation in T. cruzi. Moreover, we unveil certain differences between parasite and mammalian host tRNA editing and processing, such as cytosine-to-uridine conversion at position 32 of tRNAThrAGU in T. cruzi, that may be exploited for the identification of novel druggable targets of intervention.


[Effect of solar activity on the physiological rhythms of biological systems].
The infradian components, including those with a period of about 3.5, 7, 30 days, are ubiquitously found in biology, from unicells to complex biological organisms. It can be hypothesized that heliogeophysical factors other than the solar visible light, likely at the origin of the circadian system (with a period of about 24 hours), may be responsible for the infradian biosystems.


Family of plane solitary waves in dimer granular crystals.
Uniform planar impact on a two-dimensional square packing of spheres with intruders at interstitial locations is investigated. An equivalent one-dimensional granular chain model is proposed with appropriate scaling and is verified numerically. Numerical observations demonstrate the existence of a new family of plane solitary waves with different profiles at unique combinations of material properties. In particular, a special case of a solitary wave whose profile is similar to that of the homogeneous chains is also reported. Material combinations that cause solitary waves are systematically extracted for a wide range of material properties. For the solitary wave similar to that of a homogeneous chain, a quasicontinuum approximation is employed to predict the shape and width of the solitary wave, showing good agreement with the numerical results. Finally, an asymptotic analysis is conducted to predict the solitary wave solutions.


More agencies want to help. Directory of funders.
If you want to know who might be willing to fund your safe motherhood project, write to WHO's Maternal Health and Safe Motherhood Program for our new directory. Produced in collaboration with the UK-based development agency, AHRTAG, the Directory of funders of maternal health and safe motherhood projects has more than 70 entries, including the World Bank and many UNICEF national offices. UNDP and UNFPA wrote to us indicating that they can only respond to government requests for assistance. The directory is intended for the use of non-governmental organizations planning to extend or start safe motherhood activities. WHO regularly receives requests for support which it is unable to assist because it is not a funding agency. It was in response to this evident need that the directory was prepared. Each entry in the directory contains the name, address, telephone and fax details of the funder. One agency has indicated that it may fund a project valued at as much as US$2 million while another would consider grants for as little as US$1000. Where available, details of the types of projects considered are also included. The most popular areas of support are health education, training and community-level maternity services. Some agencies have said that they are interested in supporting national safe motherhood newsletters. If you would like to receive a free copy of the directory, or if your agency would like to be included in the next edition, please write to the Maternal Health and Safe Motherhood Program, Division of Family Health, WHO, 1211 Geneva 27, Switzerland. Good luck in finding funding for your project]


Chemical structures of hydrazine-treated graphene oxide and generation of aromatic nitrogen doping.
Chemically modified graphene platelets, produced via graphene oxide, show great promise in a variety of applications due to their electrical, thermal, barrier and mechanical properties. Understanding the chemical structures of chemically modified graphene platelets will aid in the understanding of their physical properties and facilitate development of chemically modified graphene platelet chemistry. Here we use (13)C and (15)N solid-state nuclear magnetic resonance spectroscopy and X-ray photoelectron spectroscopy to study the chemical structure of (15)N-labelled hydrazine-treated (13)C-labelled graphite oxide and unlabelled hydrazine-treated graphene oxide, respectively. These experiments suggest that hydrazine treatment of graphene oxide causes insertion of an aromatic N(2) moiety in a five-membered ring at the platelet edges and also restores graphitic networks on the basal planes. Furthermore, density-functional theory calculations support the formation of such N(2) structures at the edges and help to elucidate the influence of the aromatic N(2) moieties on the electronic structure of chemically modified graphene platelets.