Mining TCGA and GEO databases for the prediction of poor prognosis in lung adenocarcinoma based on up-regulated expression of TNS4.
To investigate the clinical significance of Tensin4 (TNS4) in human cancers, particularly lung cancer, we mined the Cancer Genome Atlas database for lung adenocarcinoma (TCGA-LUAD) and the Gene Expression Omnibus database to predict poor prognosis based on the up-regulated expression of TNS4 in LUAD. The correlation between the clinical pathologic features of patients and TNS4 gene expression was analyzed using the Wilcoxon signed-rank test. Cox regression analysis was used to evaluate the association of clinicopathologic characteristics with the overall survival (OS) of cancer patients using TCGA data. The relationship between TNS4 expression and cancer patient survival was evaluated with Kaplan-Meier survival curves and meta-analyses. GO and KEGG were also included in the data mining methods. The expression level of TNS4 in LUAD tissue was higher than that in adjacent normal tissue (P < .001). According to the Kaplan-Meier survival curve, LUAD patients with high TNS4 expression had worse prognosis than those with low TNS4 expression (P < .001 for OS; P = .028 for progression-free survival). A positive correlation between TNS4 expression and poor OS was found with both univariate and multivariate analyses. Increased TNS4 expression in LUAD was closely correlated with a higher disease stage (P = .007), positive lymph nodes (P = .005), and larger tumor size (P = .002). Moreover, meta-analysis including seven independent datasets showed LUAD patients with higher TNS4 had poorer OS (combined hazard ratio = 1.27, 95% confidence interval 1.16-1.39). In the high-TNS4 population, regulation of the actin cytoskeleton, extracellular matrix receptor interactions, and focal adhesion were differentially enriched. Integrin α6β4 and laminin-5 genes were also associated with TNS4. TNS4 expression may be a potential biomarker for predicting poor survival in LUAD. Moreover, the correlation between TNS4 and integrin α6β4 may be attributed to the role of TNS4 in LUAD.


[Homolateral Monteggia and Galeazzi fractures: a case report and review of the literature].
We report a very rare case of Monteggia and Galeazzi fractures of the same forearm in a 23-year-old female traffic accident victim. Fractures of the two forearm bones were reduced and fixed with a solid assembly. Dislocation of the radial head reduced spontaneously. Inferior radioulnar instability was treated by blocking the joint with a K wire for one month. At 24 months, outcome was satisfactory with 40 degrees pronation and 70 degrees supination. Elbow and wrist flexion-extension and muscle force were the same as on the healthy side. Surgery is indicated in this rare association in adults. As it is very important to restore exactly the anatomy with solid fixation of the ulna to achieve and maintain reduction of the radial head. Surgical exploration of the humeroradial joint is not required unless reduction cannot be achieved. The same is true for fixation of the radius after Galeazzi fracture. If an inferior radioulnar instability persists, we propose temporary stabilization with a K wire. Our experience with this case would argue against first intention resection of the distal portion of the ulna as proposed by Hughston. We prefer to postpone resection which would be performed only in case of bothersome instability. A Sauvé-Kapandji procedure would then be a possible solution.


Diagnostic evaluation of the adrenal incidentaloma: decision and cost-effectiveness analyses.
The goal of this study was to examine the clinical and economic outcomes of alternative diagnostic strategies for differentiating benign from malignant adrenal masses. We used cost-effectiveness assessment derived from decision analysis and the economic perspective of the payer of health care services. One-time evaluation with fine-needle aspiration (FNA) and combinations of chemical-shift MRI, noncontrast CT, 131I-6beta-iodomethylnorcholesterol (NP-59) scintigraphy, with or without FNA, in a hypothetical cohort of 1000 patients with incidentally discovered unilateral, nonhypersecretory adrenal masses. We calculated and compared the diagnostic effectiveness, costs and cost-effectiveness of the alternative strategies based on estimates from published literature and institutional charge data. At an assumed baseline malignancy rate of 0.25, diagnostic utility varied from 0.31 (CT0) to 0.965 (NP-59) and diagnostic accuracy from 0.655 [noncontrast CT using a cut-off attenuation value of > or = 0 (CT0)] to 0.983 (NP-59). The average cost per patient per strategy ranged from $746 (NP-59) to $1745 (MRI +/- FNA). The best and worst potential cost-to-diagnostic utility ratios were 773 (NP-59) and 2839 (CT0) and 759 (NP-59) and 1982 (MRI +/- FNA) for cost and diagnostic accuracy, respectively. The NP-59 strategy was the optimal choice regardless of the expected outcome examined: cost, diagnostic utility, diagnostic accuracy or cost-effectiveness. Varying the prevalence of malignancy did not alter the cost-effectiveness advantage of NP-59 over the other diagnostic modalities. Based on available estimates of reimbursement costs and diagnostic test performance and using reasonable clinical assumptions, our results indicate that the NP-59 strategy is the most cost-effective diagnostic tool for evaluating adrenal incidentalomas over a wide range of malignancy rates and that additional clinical studies are warranted to confirm this cost-effectiveness advantage.


Renal abnormalities and vascular complications in primary hyperaldosteronism. Evidence on tertiary hyperaldosteronism.
The frequency of underlying renal or renal artery disease, and the incidence of vascular complications were reviewed in a series of 136 cases of primary hyperaldosteronism. This was in order to investigate the possible existence of 'tertiary' hyperaldosteronism, and to examine the commonly held view that primary hyperaldosteronism is a relatively benign form of hypertension. Ten cases (7-4 per cent) had evidence of renal artery stenosis and eleven (8-1 per cent) parenchymatous renal disease. In comparison with the reported frequency in large general series of hypertensives, these data show no evidence of an excess of underlying renal disease. It is unlikely, therefore, that autonomous aldosterone secreting adenomata occur commonly as a consequence of prolonged secondary hyperaldosteronism. Four cases (2-9 per cent) had evidence of the malignant-phase of hypertension, and over a mean observation time of 5-9 years, 31 cases (22-8 per cent) developed 39 vascular complications. It appears, therefore, that vascular complications are not rare in primary hyperaldosteronism, and early and effective treatment is thus necessary.


Top-down and bottom-up influences on demographic rates of Antarctic fur seals Arctocephalus gazella.
Two major drivers in population dynamics are bottom-up processes, such as environmental factors that affect foraging success, and the top-down impacts of predation. Many populations of marine mammal and seabird species appear to be declining in response to reductions in prey associated with the bottom-up effects of climate change. However, predation, which usually occurs at sea and is difficult to observe, may also play a key role. We analysed drivers of population dynamics of Antarctic fur seals Arctocephalus gazella at Cape Shirreff from 1997 to 2009, including a predator that targets pre-weaned pups and bottom-up environmental effects in an ecosystem particularly sensitive to small changes in temperature. We use Bayesian mark-recapture analysis to demonstrate that although large-scale environmental variability affects annual adult survival and reproduction, first year survival appears to be driving the current decline in this population (as defined by a decline in the annual number of pups born). Although the number of pups increased during the first third of the study, first year survival and recruitment of those pups in later years was very low. Such low survival may be driven by leopard seal Hydrurga leptonyx predation, particularly prior to weaning. Our results suggest that without leopard seal predation, this population would most likely increase in size, despite the observed bottom-up effects of climate changes on adult vital rates. More broadly, our results show how age-targeted predation could be a major factor in population decline of K-selected colonial breeders.


Role of dopamine transporter imaging in the diagnosis of atypical tremor disorders.
Dopamine transporter (DAT) imaging detects presynaptic dopamine neuronal dysfunction and thereby assists differentiation of conditions with and without dopamine deficit. In atypical tremor disorders, DAT imaging can differentiate between Parkinson's disease (PD), where dopamine deficit is demonstrated on DAT imaging, and essential tremor, where no dopamine deficit is found. DAT imaging may be particularly informative in monosymptomatic rest tremors, benign tremulous Parkinson's syndrome, and in the elderly in whom essential tremor may be accompanied by pseudoparkinsonism.


A Randomized Controlled Study Addressing Dexamethasone Tolerability in the Treatment of Acute Asthma in Children: Mary Poppins on Trial!
AimEmesis of oral medications continues to be a problem in the management of acute pediatric asthma exacerbations; therefore, we set out to assess whether smaller volumes of oral dexamethasone resulted in better tolerability. Methods: Children aged 2-14 years, presenting to the emergency department with acute asthma exacerbation, were enrolled in this open, prospective randomized controlled trial. Participants received 0.3 mg/kg of dexamethasone in either its concentrated volume (10 mg/mL) or mixed with Ora Sweet (1 mg/mL). Tolerability was measured by vomiting within 45 minutes of receiving dexamethasone, with stratification, a priori, for prior vomiting. Results: 430 participants were enrolled. 23/213 (11%) in the 10 mg/mL group vomited dexamethasone compared to 16/217 (7%) in the 1 mg/mL group (P = .29). 11/179 (6%) in the 10 mg/mL group vomited compared to 8/183 (3%) in the 1 mg/mL group (.61). For those 68 stratified with prior vomiting, 12/34 (35%) in the 10 mg/mL group vomited compared to 8/34 (24%) in the 1 mg/mL group (P = .43). None of these results were statistically different. Prior vomiting increased the risk of vomiting, regardless of the formulation given (P < .001). Conclusions: Volume does not play a significant role in the tolerability of dexamethasone. Therefore, palatability should not be sacrificed for a smaller volume of dexamethasone to improve tolerability.


Perspectives on cognitive neuroscience.
How is it that we can perceive, learn and be aware of the world? The development of new techniques for studying large-scale brain activity, together with insights from computational modeling and a better understanding of cognitive processes, have opened the door for collaborative research that could lead to major advances in our understanding of ourselves.


Isolated central nervous system arteriopathy with multiple aneurysms in an adolescent. A case report.
A 17-year-old male suffered recurrent subarachnoid hemorrhages due to multiple aneurysms in the distal branches of the cerebral arteries. Autopsy revealed arteriopathy as well as the aneurysms. The arteriopathy was widespread, affecting the distal branches of small and medium-sized muscular cerebral arteries, as well as the anterior and posterior spinal arteries, and vasocorona. The arteriopathy was characterized by prominent intimal thickening, discontinuity or absence of the internal elastic lamina, and thinning and/or disappearance of smooth muscle in the tunica media with fibroplasia. Slight intimal thickening was also observed in the arteries of the circle of Willis and its major branches, as well as in the basilar artery. However, the arterioles, venules and veins showed no remarkable features. The arterial lesions were found only in the central nervous system. The multiple aneurysms in the distal branches of the cerebral arteries, which had produced the main symptoms and clinical signs, were due to the arteriopathy.


Evidence for the D-cell of the pancreas secreting somatostatin.
By immunofluorescence, somatostatin-, glucagon- and insulin-containing cells are localized in serial sections of the pigeon pancreas. The distribution of the somatostatin immunofluorescent-cells corresponds to that of the D-cells (A1-cells), which are particularly numerous in this animal species. This observation, coupled with the finding of D, A and B-cells at the ultrastructural level, indicates that the D-cell is responsible for the secretion of somatostatin.


Transforming growth factor-beta1 gene transfer is associated with the development of regulatory cells.
Adenovirus-mediated transfection of mouse cardiac allografts with active human transforming growth factor-beta 1 (TGF-beta1) prolongs transplant survival provided that recipients are initially depleted of CD8+ T cells. To test if graft survival was prolonged by persistent TGF-beta1 transgene expression, long-term transfected allografts were re-transplanted into naïve mice that were transiently depleted of CD8+ T cells. Re-transplanted allografts were acutely rejected, indicating that TGF-beta1 transgene expression did not suppress effector cell function. We next asked whether TGF-beta1 gene transfer was associated with the development of regulatory cells. When splenocytes obtained from mice bearing long-term TGF-beta1-transfected allografts were adoptively transferred into recipients of non-transfected cardiac allografts, prolonged allograft survival was observed, and increased levels of the regulatory T cell transcription factor Foxp3 were present. To further test for regulation, differentiated effector cells were obtained from mice that had rejected cardiac allografts and were adoptively transferred into mice bearing long-term TGF-beta1 transfected cardiac allografts. The effector cells failed to mediate rejection in mice bearing TGF-beta1-transfected allografts and we observed a significant increase in intra-graft Foxp3 expression. These findings indicate that TGF-beta1 gene transfer allows for the development of regulatory cells that control graft-reactive T cell responses once therapeutic levels of the transgene product are no longer produced.


Increased incidence of monoclonal B-cell infiltrate in chronic myeloproliferative disorders.
A total of 106 trephine biopsy specimens with clinical, laboratory and pathology findings corresponding to chronic myeloproliferative disorders (CMPD) were analyzed to reveal the nature of the lymphoid infiltrate in the bone marrow. Histological investigation in 31 chronic myeloid leukemia (CML), 29 CMPDs not otherwise specified (CMPD-NOS), 28 essential thrombocytosis (ET), 15 polycythemia vera (PV) and three chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES) exhibited in 32% various amounts of lymphocytic infiltrate of sparsely to moderately diffuse or nodular types in the bone marrow, but the reactive or coinciding lymphomatous nature could not be revealed by histology alone in the majority of cases. PCR analysis of the immunoglobulin heavy chain (IgH) gene rearrangement was successfully performed in 81 out of the 106 DNA specimens extracted from formol-paraffin blocks. Out of the 81 samples with good-quality DNA, 18 gave a single or double discrete amplification band(s), which was reproducible only in four specimens. Sequencing finally proved monoclonal B-cell population of both pre- and postfollicular origin in all four samples (5%), one CML and three CMPD-NOS. Detailed clinical and pathological investigations indicated overt B-cell malignant lymphoma with clonal relationship to the CMPD in two out of these four patients. We conclude that detailed molecular analysis of IgH gene rearrangement in bone marrow samples of CMPD patients is needed to identify the true monoclonal B-cell infiltration, which-even without overt malignant lymphoma-may occur in this group of disorders. Modern Pathology (2004) 17, 1521-1530, advance online publication, 16 July 2004; doi:10.1038/modpathol.3800225.


Red cell indices in classification and treatment of anemias: from M.M. Wintrobes's original 1934 classification to the third millennium.
Measurements of red cell volume, hemoglobin (Hb) concentration and Hb content continue to play a crucial role in the differential diagnosis of anemias 80 years after the publication of Wintrobe's seminal work. Modern hematology analyzers provide additional data on the heterogeneity of these parameters (distribution width) and quantify similar parameters of reticulocytes as well. Red cell and reticulocyte cellular indices are widely used in the diagnosis and monitoring of hematological diseases. Quantification of hypochromic cells is valuable in the differential diagnosis of thalassemia trait and iron deficiency, and in monitoring therapeutic response to erythropoietic stimulating agents, while hyperchromic cells are an essential diagnostic component for hereditary spherocytosis and may correlate with hemolytic parameters in sickle cell disease. Values for these parameters however depend on the technology used. Red cell clearance is associated with a reduction in both Hb content and cell volume: normal cells are likely to be removed by the time they reach a volume of 72 fl. Reticulocyte parameters such as Hb content (CHr or ret-He) or maturity index (RMI) have shown value in a variety of hematological conditions. New findings from genetic association studies have identified several potential novel genes affecting red cell indices, which are not mediated by changes in iron availability. Red cell indices continue to provide an essential support to the diagnosis and monitoring of hematological diseases.


Respiratory Mites ( Orthohalarachne diminuata) and β-hemolytic Streptococci-Associated Bronchopneumonia Outbreak in South American Fur Seal Pups ( Arctocephalus australis).
Although mites of the Orthohalarachne genus are common parasites of otariids, their role as agents of disease and in causing population-level mortality is unknown. In the austral summer of 2016, there was an increase in mortality among South American fur seal ( Arctocephalus australis) pups at Guafo Island, Northern Chilean Patagonia. Pups found dead or terminally ill had moderate to marked, multifocal, mucopurulent bronchopneumonia associated with large numbers of respiratory mites ( Orthohalarachne diminuata) and rare Gram-positive cocci. In lung areas less affected by bronchopneumonia, acute interstitial pneumonia with marked congestion and scant hemorrhage was evident. Bacteria from pups dying of bronchopneumonia were isolated and identified as Streptococcus marimammalium and Streptococcus canis. Respiratory mites obstructed airflow, disrupted airway epithelial lining, and likely facilitated the proliferation of pathogenic β-hemolytic streptococci, leading to severe bronchopneumonia and death of fur seal pups. An abrupt increase in sea surface temperature in Guafo Island corresponded to the timing of the bronchopneumonia outbreak. The potential role of environmental factors in the fur seal pup mortality warrants further study.


Tritium and 14C isotope effects using tracers of leucine and alpha-ketoisocaproate.
To test if different leucine tracers behave in an indistinguishable manner and, by implication, that their metabolism is identical to that of natural leucine, we measured whole body leucine turnover in dogs and humans and fibrinogen synthesis in dogs by simultaneously infusing either [1-14C]leucine or [4,5-3H]leucine or [1-14C]alpha-ketoisocaproate (KIC) and [4,5-3H]KIC. Whole body leucine fluxes calculated from the plasma specific activity of the transaminated product of the infused tracer (reciprocal pool model) were lower (dogs by 5.7%; humans by 6.4%, both P < 0.02) when the plasma 3H specific activity compared to 14C specific activity were used with leucine tracers and were also lower (dogs by 4.4%, P < 0.02; humans by 8.6%, P < 0.06) using the KIC tracers. Using leucine or KIC tracers in dogs, the fractional rate of fibrinogen synthesis was 6.7% or 9.4% lower, respectively, (P < 0.02) using the 3H versus the 14C tracer. The apparently lower incorporation of 3H into protein was only in part accounted for by detritiation (2.1%, P = 0.05) of [3H]leucine during acid hydrolysis of proteins. These results suggest that in vivo and/or in vitro differential isotope effects are small (approximately 5%), but should be considered when dual isotopes infusions are employed to partition amino acid metabolism.


Oxygen reduces accumulation of type IV collagen in endothelial cell subcellular matrix via oxidative stress.
Anchorage-dependent cells in culture attach initially to proteins adsorbed to the culture substrate from the medium, and produce and deposit a subcellular matrix during the course of the cultivation. The aim of this study was to determine whether the concentration of O(2) in the culture atmosphere affects the accumulation of type IV collagen and laminin under human endothelial-cell monolayers. Enzyme-linked immunoassays on decellularized polystyrene substrates showed less type IV collagen, but not less laminin, under cells incubated in the standard atmosphere (5% CO(2) in air, i.e., approximately 20% O(2)) compared to an atmosphere of 5% O(2) and 5% CO(2) in N(2). Type IV collagen accumulation was inhibited via oxidative stress, because the inhibitory effect of 20% O(2) was antagonized by antioxidant ascorbic acid, and mimicked by prooxidant pyrogallol and exogenous H(2)O(2). Measurements of endogenous H(2)O(2) accumulation demonstrated that endothelial cells partially adapt to the high O(2) concentration. These results may have implications in endothelium modeling in vitro and in engineering of endothelial cell sheets and endothelialized vascular grafts.


Primary endometrial squamous cell carcinoma with extensive squamous metaplasia and dysplasia.
Primary squamous cell carcinoma of endometrium is a rare entity. Only 64 cases have been documented in the literature. We report a case of 60-year-old postmenopausal woman who presented with abdominal distention and blood-stained vaginal discharge for 6-7 months. Clinically, chronic pyometra was considered. Total abdominal hysterectomy was performed and histopathologically, it was diagnosed as a case of primary squamous cell carcinoma of endometrium with extensive squamous metaplasia and dysplasia.


Discrete-time quantum walk dispersion control through long-range correlations.
We investigate the evolution dynamics of inhomogeneous discrete-time one-dimensional quantum walks displaying long-range correlations in both space and time. The associated quantum coin operators of internal states are built to exhibit random inhomogeneity distribution of long-range correlations embedded in the time evolution protocol through a fractional Brownian motion with spectrum following a power-law behavior, S(k)∼1/k^{ν}. From extensive numerical simulations with averages over a large number of independent realizations of the phases of quantum coins, the power-law correlated disorder encoded in the coin phases is shown to give rise to a wide variety of spreading patterns of the qubit states, from localized to subdiffusive, diffusive, and superdiffusive (including ballistic) behavior, depending on the relative strength of the parameters driving the correlation degree. Dispersion control is possible in one-dimensional discrete-time quantum walks by tuning the long-range correlation properties assigned to the inhomogeneous quantum coin operator.


Various Approaches and Treatments for Pelvic Organ Prolapse in Women.
Pelvic organ prolapse (POP) is bulging of one or more of the pelvic organs into the vagina and triggered by multiple causes. It is a very common disorder, especially among older women. POP is characterized by protrusion of the presentation part visible by the naked eye, and problems with urination or bowel movements. POP can be diagnosed based on the onset of symptoms and a pelvic exam, and management options include medical and surgical treatment. Although medical treatment cannot correct the abnormal herniation of the pelvic structures, this can help alleviate symptoms. One of the disadvantages of surgical interventions is recurrence, and advances in surgical techniques have decreased recurrence rates of POP. Therefore, author will explain the gynecology and urology approach and treatment.


Hydrogen-bonding alterations of the protonated Schiff base and water molecule in the chloride pump of Natronobacterium pharaonis.
Halorhodopsin is a light-driven chloride ion pump. Chloride ion is bound in the Schiff base region of the retinal chromophore, and unidirectional chloride transport is probably enforced by the specific hydrogen-bonding interaction with the protonated Schiff base and internal water molecules. In this article, we study hydrogen-bonding alterations of the Schiff base and water molecules in halorhodopsin of Natronobacterium pharaonis (pHR) by assigning their N-D and O-D stretching vibrations in D(2)O, respectively. Highly accurate low-temperature Fourier transform infrared spectroscopy revealed that hydrogen bonds of the Schiff base and water molecules are weak in the unphotolyzed state, whereas they are strengthened upon retinal photoisomerization. Halide dependence of the stretching vibrations enabled us to conclude that the Schiff base forms a direct hydrogen bond with Cl(-) only in the K intermediate. Hydrogen bond of the Schiff base is further strengthened in the L(1) intermediate, whereas the halide dependence revealed that the acceptor is not Cl(-), but presumably a water molecule. Thus, it is concluded that the hydrogen-bonding interaction between the Schiff base and Cl(-) is not a driving force of the motion of Cl(-). Rather, the removal of its hydrogen bonds with the Schiff base and water(s) makes the environment around Cl(-) less polar in the L(1) intermediate, which presumably drives the motion of Cl(-) from its binding site to the cytoplasmic domain.


Gene-product relationships of fhlA and fdv genes of Escherichia coli.
Synthesis of formate dehydrogenase coupled to formate hydrogenlyase activity in Escherichia coli was found to require the product of the fhlA gene. Transcription of fdhF, the gene coding for the 80-kilodalton (kDa) selenopeptide of formate dehydrogenase, was not detected in an fhlA genetic background. Mutations in the fhlA gene also abolished production of the hydrogenase activity associated with formate hydrogenlyase activity. The fhlA gene resides next to the hydB gene at 59 min in the E. coli chromosome, and the two genes are transcribed in opposite directions. The fhlA gene codes for a 78-kDa protein. A neighboring gene, fdv, codes for an 82-kDa protein, and the physiological role of this gene product is unknown, although a role in H2 metabolism can be detected.


Phylogenetic analyses suggest lateral gene transfer from the mitochondrion to the apicoplast.
Apicomplexan protozoa contain a single mitochondrion and a multimembranous plastid-like organelle termed apicoplast. The size of the apicomplexan plastid genome is extremely small (35 kb) thus offering a limited number of genes for phylogenetic analysis. Moreover, the sequences of apicoplast genes are highly adenosine+thymidine-rich and rapidly evolving. Due to these facts, phylogenetic analyses based on different genes or the structure of the ribosomal operon show conflicting results and the evolutionary history of this exciting organelle remains unclear. Although it is evident that the apicoplast and its genome is plastid-derived, our detailed phylogenetic analysis of amino acid and nucleotide sequences of selected apicoplast ribosomal protein genes rpl2, rpl14 and rps12 show their possible mitochondrial origin. The affinity of apicoplast ribosomal proteins to their mitochondrial homologs is very stable and well supported. Based on our results we propose that apicoplasts might contain both plastid and mitochondrial genes, thus constituting a hybrid assembly.


An Alternative Promoter in Intron1 of the Renin Gene is Regulated by Glucose Starvation via Serum Response Factor.
Renin is known as a secretory glycoprotein that ultimately leads to angiotensin II generation. In this way renin exerts pro-inflammatory effects and promotes cardiac injury. Additional transcripts have been identified encoding for a cytosolic renin isoform that - in contrast to secretory renin - exhibits cardioprotective effects under ischemic conditions. The promoter of these transcripts is unknown. Using qRT-PCR and dual-luciferase reporter assay we examined the expression and promotor activity of cytosolic renin as well as the regulation by glucose starvation in H9c2 cardiomyoblasts. We identified a promoter in intron1 of the rat renin gene with two glucose starvation-sensitive regions. One region contains a binding motif for serum response factor (SRF). Under glucose depletion expression of SRF increased prior to cytosolic renin. SRF knock down selectively decreased cytosolic renin expression and attenuated the increase of cytosolic renin expression under glucose depletion. Transcripts encoding for secretory and cytosolic renin are differentially expressed. The low basal expression of cytosolic renin as well as its induction under ischemia-related conditions represents an efficient system regulated in accordance with its previously identified unfavorable effects under control situations but protective effects seen after myocardial infarction or glucose depletion.


Activity of medullary reticulospinal neurons during fictive locomotion.
1. The pattern of discharge of medullary reticulospinal neurons, identified by antidromic stimulation applied at the L1-L2 segment of the spinal cord, was studied during fictive locomotion, occurring spontaneously, or evoked by stimulation of the mesencephalic locomotor region in high-decerebrate, paralyzed cats. Unitary recordings were made in the medial reticular formation (P5.0-14.0 mm; L0.5-2.0 mm), and the fictive locomotor pattern was monitored by recording the electroneurogram (ENG) of representative flexor and extensor muscle nerves from each of the four limbs. 2. In total, 117 reticulospinal neurons were recorded in 15 cats. Among these, 73.5% (86/117) modified their discharge at the onset of locomotion. These cells were divided into three subpopulations: 34/86 of the cells always maintained a fixed temporal relationship with the activity of one of the recorded nerves (ENG-related = 39.6%); the pattern of discharge of 42/86 cells was related to the locomotor rhythm [(LR-related-48%)] but was not temporally correlated with any of the recorded nerves; and the remaining 10 cells increased their firing frequency at the onset of locomotion but remained tonic (TONIC-11.6%). 3. Of the ENG-related neurons, 64.8% were temporally correlated to extensor nerve activity, whereas the remaining 35.2% were correlated to flexor nerves. These neurons were either related to forelimb (55.9%) or hindlimb (44.1%) nerves lying either ipsilateral (38.2%) or contralateral (61.8%) to the recording site. A few neurons (n = 3; 8.8%) were related to nerve activity of more than one limb. 4. The pattern of discharge of the LR-related neurons, although not correlated to the activity of any one recorded nerve, could be preferentially related to the locomotor rhythm in either the forelimbs (12/23) or hindlimbs (11/23). 5. ENG- and LR-related reticulospinal neurons were intermingled in the medial reticular formation. In both cases, cells related to the forelimbs were located more dorsally than those related to the hindlimbs. It is suggested that both the ENG- and LR-related neurons represent a single functional population of reticulospinal neurons that is part of an intrinsically organized reticulospinal system that functions to coordinate the activity of the skeletal musculature. 6. The present results show that the majority of reticular neurons projecting as far as the lumbar spinal cord are phasically modulated during locomotion, even in the absence of phasic peripheral afferent inputs. Moreover, the complexity of the discharge patterns in paralyzed animals was found to be similar to that observed in the intact cat.(ABSTRACT TRUNCATED AT 400 WORDS)


Discovery of New SIRT2 Inhibitors by Utilizing a Consensus Docking/Scoring Strategy and Structure-Activity Relationship Analysis.
SIRT2, which is a NAD+ (nicotinamide adenine dinucleotide) dependent deacetylase, has been demonstrated to play an important role in the occurrence and development of a variety of diseases such as cancer, ischemia-reperfusion, and neurodegenerative diseases. Small molecule inhibitors of SIRT2 are thought to be potential interfering agents for relevant diseases. Discovery of SIRT2 inhibitors has attracted much attention recently. In this investigation, we adopted a consensus docking/scoring strategy to screen for novel SIRT2 inhibitors. Structural optimization and structure-activity relationship (SAR) analysis were then carried out on highly potent compounds with new scaffolds, which led to the discovery of 2-((5-benzyl-5H-[1,2,4]triazino[5,6-b]indol-3-yl)thio)-N-(naphthalen-1-yl)acetamide (SR86). This compound showed good activity against SIRT2 with an IC50 value of 1.3 μM. SR86 did not exhibit activity against SIRT1 and SIRT3, implying a good selectivity for SIRT2. In in vitro cellular assays, SR86 displayed very good antiviability activity against breast cancer cell line MCF-7. In Western blot assays, SR86 showed considerable activity in blocking the deacetylation of α-tubulin, which is a typical substrate of SIRT2. Collectively, because of the new scaffold structure and good selectivity of SR86, it could serve as a promising lead compound, hence deserving further studies.


Prevention of cholesterol-induced gallstones by hyodeoxycholic acid in the prairie dog.
Prairie dogs of both sexes were fed a semisynthetic diet containing 0.35% cholesterol for a period of 8 weeks. This lithogenic diet induced cholesterol gallstones in ten "lithogenic control animals", five males and five females. Three animals maintained with a high glucose, fat-free diet did not develop gallstones although the cholesterol saturation of their bile approached unity. The formation of gallstones was prevented in four out of five males and all five females fed the lithogenic diet plus 0.1% hyodeoxycholic acid (30 mg per kg body weight per day). The biles of the prairie dogs receiving hyodeoxycholic acid were abnormally colored, cloudy, and highly saturated with cholesterol but contained neither cholesterol crystals nor gallstones (with the exception of one male). Feeding the relatively hydrophilic bile acid, hyodeoxycholic acid, was associated with an increase in hepatic microsomal HMG-CoA reductase activity. Cholesterol 7 alpha-hydroxylase, on the other hand, was inhibited by the administered bile acid. The dietary hyodeoxycholic acid was transformed, in part, to 3 alpha, 6 beta-dihydroxy-5-beta-cholanoic acid and hyocholic acid. It is concluded that hyodeoxycholic acid and its metabolites did not prevent the induced cholelithiasis by causing a decrease in the concentration of biliary cholesterol. Instead, this hydrophilic bile acid apparently increases the amount of cholesterol in the bile, probably in the form of a liquid crystalline mesophase. Hyodeoxycholic acid apparently prevents gallstones by preventing the nucleation and aggregation of cholesterol crystals. The lithogenic diet induced moderate to marked bile duct proliferation together with portal fibrosis and inflammatory infiltration. The addition of hyodeoxycholic acid to the lithogenic diet reduced all of the portal tract changes.


Determinants of food rejection amongst school children.
This study investigates the role of food preferences in food rejection amongst primary school children. A total of 17 children (9- and 10-year-old) took part in group discussions from which elicited their preferences from 35 photographs of different foods and dishes. They also discussed their reasons for rejecting a specific meal that had been offered to them during a trip to France. The results showed that their food preferences played a limited role in their rejection. They reported to be disgusted by the meal, and this apparently stemmed from stereotype of French food associated with imagination and miscommunication. They also described aspects of the food as unfamiliar.


Mapping of PCR-based markers for mouse chromosome 4 on a backcross penetrant for the misty (m) mutation.
A genetic linkage map for mouse Chromosome (Chr) 4 (MMU 4) has been constructed with an intersubspecific backcross between the C57BL/KsJ strain homozygous for the misty (m) coat color locus and the inbred Mus musculus musculus Czech II strain. Several recently developed PCR-based simple sequence length polymorphism (SSLP) markers have been intercalated among gene-based markers including six anchor loci on mouse Chr 4 to assemble this map. Marker order and genetic distances are similar to the composite genetic linkage map compiled from crosses between a variety of other inbred and feral mouse strains. Transmission ratio distortion in favor of feral alleles is apparent for a region of distal MMU 4. In addition, the misty phenotype is more fully penetrant in the present backcross than in other reported interspecific and intersubspecific crosses. Backcrosses employing inbred Mus musculus musculus strains may allow reliable phenotyping and mapping of mouse mutations displaying complex phenotypes with incomplete and/or ambiguous penetrance on other feral genetic backgrounds.


Myocardial infarction triggers chronic cardiac autoimmunity in type 1 diabetes.
Patients with type 1 diabetes (T1D) suffer excessive morbidity and mortality after myocardial infarction (MI) that is not fully explained by the metabolic effects of diabetes. Acute MI is known to trigger a profound innate inflammatory response with influx of mononuclear cells and production of proinflammatory cytokines that are crucial for cardiac repair. We hypothesized that these same pathways might exert "adjuvant effects" and induce pathological responses in autoimmune-prone T1D hosts. Here, we show that experimental MI in nonobese diabetic mice, but not in control C57BL/6 mice, results in a severe post-infarction autoimmune (PIA) syndrome characterized by destructive lymphocytic infiltrates in the myocardium, infarct expansion, sustained cardiac autoantibody production, and T helper type 1 effector cell responses against cardiac (α-)myosin. PIA was prevented by inducing tolerance to α-myosin, demonstrating that immune responses to cardiac myosin are essential for this disease process. Extending these findings to humans, we developed a panel of immunoassays for cardiac autoantibody detection and found autoantibody positivity in 83% post-MI T1D patients. We further identified shared cardiac myosin autoantibody signatures between post-MI T1D patients and nondiabetic patients with myocarditis, which were absent in post-MI type 2 diabetic patients, and confirmed the presence of myocarditis in T1D by cardiac magnetic resonance imaging techniques. These data provide experimental and clinical evidence for a distinct post-MI autoimmune syndrome in T1D. Our findings suggest that PIA may contribute to worsened post-MI outcomes in T1D and highlight a role for antigen-specific immunointervention to selectively block this pathway.


An overview of the epidemiology and emergence of influenza A infection in humans over time.
In recent years multiple novel influenza A strains have emerged in humans. We reviewed publically available data to summarise epidemiological characteristics of distinct avian influenza viruses known to cause human infection and describe changes over time. Most recently identified zoonotic strains have emerged in China (H7N9, H5N6, H10N8) - these strains have occurred mostly in association with visiting a live bird market. Most zoonotic AIVs and swine influenza variants typically cause mild infections in humans however severe illness and fatalities are associated with zoonotic H5N6, H10N8, H7N9 and H5N1 serotypes, and the H1N1 1918 Spanish Influenza. The changing landscape of avian influenza globally indicates a need to reassess the risk of a pandemic influenza outbreak of zoonotic origin.


Technical considerations of a new technique for orthotopic heart transplantation. Total excision of recipient's atria with bicaval and pulmonary venous anastomoses.
An alternative technique for orthotopic heart transplantation is described. It consists of total excision of the recipient's atria with donor heart transplantation performed using bicaval end-to-end anastomosis, as well as pulmonary venous anastomoses. Thus, total atrial as well as ventricular transplantation is performed. This new surgical approach is technically simple and preserves the anatomic size, geometric configuration and physiologic function of the atria. This technique has the potential to improve the long-term hemodynamic results in heart transplant patients as it reduces the incidence of postoperative atrioventricular valve regurgitation. In addition, the incidence of early posttransplant bradyarrhythmias (within 4 to 6 weeks after transplantation) that require the insertion of a permanent pacemaker is also significantly reduced. This report describes some technical guidelines for harvesting the donor heart, as well as for the implantation of the cardiac allograft, in order to avoid the development of serious intraoperative and postoperative complications directly associated with this technique.


E-cigarette use-associated lung injury (EVALI).
The prevalence of vaping has overtaken conventional cigarettes as the most frequent form of nicotine consumption among 15-24-year olds. There are currently a large number of both legitimate and illegitimate products and suppliers offering more than 8000 different flavors of vape on the market, whose additives are not tested, studied or regulated and whose safety and toxicity profile remains unknown. In vitro studies have demonstrated a dose-dependent decrease in the viability of normal human bronchial epithelial cells after exposure to vapor from electronic vape devices.Short- and medium-term studies to date indicate that vapor-induced pulmonary lesions are the most serious and commonly reported side effect; such lesions include bilateral ground glass opacities in lung bases with subpleural preservation, bilateral infiltrates, pleural effusion, pneumomediastinum and nodular opacities. Cases of EVALI have been described in patients with daily exposure, as well as in users who reported having been exposed to these substances at least once a month. The most frequently inhaled substances are THC, flavored liquids of unknown content, and nicotine.The clinical manifestations of dyspnea and cough are the most frequent respiratory symptomatology, in addition to constitutional manifestations such as fever and chills, and gastrointestinal manifestations such as vomiting, nausea, abdominal pain and diarrhea. To these can be added the presence of tachypnea, tachycardia, elevated blood pressure, hypoxia, leukocytosis with neutrophilia and elevated ESR.


The prevalence of anticardiolipin antibodies in a healthy elderly population and its association with antinuclear antibodies.
The presence of anticardiolipin antibodies (aCL) has been associated with arterial and venous thrombotic events in connective tissue diseases. Previous investigations have suggested an increased incidence of aCL in the elderly population. We have studied the prevalence of aCL in large groups of 300 healthy elderly (mean age 70) and 543 younger subjects. aCL were determined by ELISA for the presence of IgG and IgM antibodies and was detected in 37 individuals (12%). This compared with an overall prevalence in a younger population of 2%. In addition, aCL was detected in 23% of elderly individuals who were also positive test for antinuclear antibodies (ANA). There was, however, no correlation with the presence of rheumatoid factor or lymphocytotoxic antibodies in this elderly group. Therefore, aCL have increased prevalence in an elderly population, and were associated with a positive test for ANA.


The impact of advances in radiologic biliary imaging on the diagnosis of obstructive jaundice. Comparative analysis of two groups of patients hospitalized at a 5-year interval.
The study evaluates the impact of advances in biliary imaging techniques on the accuracy and rapidity of diagnosis in patients with obstructive jaundice. Two series of patients hospitalized at an interval of 5 years in the same clinic were prospectively analyzed. In both series, the results of ultrasonography (US) and percutaneous transhepatic cholangiography (PTC) were compared with the intraoperative findings. The performances of US in the assessment of ductal dilatation and choledocholithiasis significantly improved during this period. The fine-needle biopsies taken from the solid masses in liver or pancreatic parenchyma under US guidance in the second series of patients contributed to the greater proportion of correct preoperative diagnoses in this group. The number of PTC investigations increased in the second group (p less than 0.001) given the clinicians' confidence in the safety and easy performance of this method. Using both methods, the etiology of biliary obstruction was correctly diagnosed preoperatively in 85.2 per cent of the second series of patients, significantly more frequently than in the first series of patients (62.7 per cent) (p less than 0.05). The mean period in hospital necessary for the diagnosis decreased during the period analyzed from 15.4 +/- 10.8 days to 10.2 +/- 7.8 days (p less than 0.05), a fact with direct impact on the course of disease, and also on the hospital costs.


[Analysis and evaluation of nutrient composition of Ophiopogonis Radix in Santai area].
Ophiopogon japonicus is one of the commonly used medicines,and it has gradually become a therapeutic food for people's daily health care. O. japonicus in Sichuan province is the famous Dao-di herbs in Sichuan province,and is mainly produced in Santai county,Sichuan province. With the unique geographical advantage,Santai county plans to declare the new food raw materials of O. japonicus based on the geographical indication products( Fu Cheng O. japonicus),so it is necessary to analyze and evaluate the nutritional components of O. japonicus in Santai county. The experimental results showed that the content of the nutrients was characterized by low fat,high polysaccharide,high potassium and high vitamin B2,which can be developed as new food raw materials.


Granulomatous panniculitis and Hodgkin's disease.
An anergic patient with arrested Hodgkin's disease developed a cutaneous granulomatous panniculitis, an unusual dermatologic manifestation of this tumor. These granulomatous cutaneous lesions were composed primarily of epithelial cells and were free of necrosis. In contrast, focal necrotic areas were present in the granulomas detected two years previously in the original lymph node biopsy examination.


Extracorporeal treatment with high-volume continuous venovenous hemodiafiltration and charcoal-based sorbent hemoperfusion for severe metformin-associated lactic acidosis.
We present a case of a 49-year-old female with an alleged history of ingestion of approximately 100 tablets of metformin (850 mg each). Investigations revealed severe lactic acidosis with lactate levels of 13.5 mmol/L and pH of 7.17. This indicates severe toxicity and is associated with a high mortality. Charcoal-based sorbent hemoperfusion was done as a desperate effort, as patient continued to deteriorate despite supportive care and high-volume continuous venovenous hemodiafiltration. The patient survived despite metformin-associated lactic acidosis related to severe metformin toxicity.


Expression of mmu-miR-96 in the endometrium during early pregnancy and its regulatory effects on stromal cell apoptosis via Bcl2.
Decidualization of endometrial stromal cells is an important feature of implantation and pregnancy. The molecular mechanism underlying decidualization remains unclear, particularly regarding the microRNA (miRNA/miR) regulation of this process. The present study revealed the temporal and spatial distribution of mmu‑miR‑96 in the mouse uterus during early pregnancy by reverse transcription‑quantitative polymerase chain reaction and in situ hybridization. In addition, primary stromal cells were isolated from the mouse uterus and used to explore the role of mmu‑miR‑96 in decidualization. The results demonstrated that mmu‑miR‑96 was highly expressed in stromal cells during pregnancy, and was upregulated at implantation sites. In addition, mmu‑miR‑96 was strongly expressed during decidualization, which indicates that it may serve a role in the decidualization of stromal cells. Based on existing reports, mmu‑miR‑96 participates in apoptosis; therefore the present study investigated its effects on the apoptosis of primary endometrial stromal cells. The results indicated that overexpression of mmu‑miR‑96 may induce apoptosis of stromal cells. In further studies regarding the underlying mechanism, the target genes of mmu‑miR‑96 were screened by bioinformatics analysis, and it was confirmed that B‑cell lymphoma 2, an anti‑apoptotic gene, was the target of mmu‑miR‑96, as determined using a reporter gene assay. In conclusion, the present study suggested that mmu‑miR‑96 participates in the decidualization of endometrial stromal cells in mice, thereby serving a key role in pregnancy.


[Cloning and transcriptional regulation analysis of amelogenin promoter in different cells].
To clone different promoter region of amelogenin gene and analyze their transcriptional activity. The upstream regulation sequences of amelogenin gene were retrieved and analyzed. Amplified by PCR from the genomic DNA of mouse C57BL/6J and digested with restriction endonucleases enzyme, different transcriptional regulation sequences of 5'flanking of amelogenin gene including the basal promoter were cloned and ligated with luciferase gene in PGL3-Basic vector. These report vectors were transiently transfected into CHO, Hela and UMR-106 cells and luciferase assay was performed to analyse the transcription activation of these promoters. 6 promoters different in length were cloned. The activity of luciferase was very strong in Hela cells. On the contrary, the CHO and UMR-106 cells showed weak fluorescence. Luciferase activity fluctuated with the different promoter lengths in Hela cell as well as in CHO and UMR-106 cells. 975 bp and 532 bp of amelogenin 5'flanking DNA had a strong transcriptional activation, but 285 bp of amelogenin 5'flanking DNA had a weaker transcriptional activation. The sequence of amelogenin promoter can be activated in Hela cell. Hela cell can be used as a good model to study the transcriptional regulation of amelogenin promoter. According to the different activities of different lengths, it is suggested that there were some potential siliencer located between -975 and -532, and some potential activator in the region between -532 and -285.


Environmental surveillance identifies multiple introductions of MRSA CC398 in an Equine Veterinary Hospital in the UK, 2011-2016.
Bacterial environmental and surgical site infection (SSI) surveillance was implemented from 2011-2016 in a UK Equine Referral Veterinary Hospital and identified 81 methicillin-resistant Staphylococcus aureus (MRSA) isolates. A cluster of MRSA SSIs occurred in early 2016 with the isolates confirmed as ST398 by multilocus sequence typing (MLST), which prompted retrospective analysis of all MRSA isolates obtained from the environment (n = 62), SSIs (n = 13) and hand plates (n = 6) in the past five years. Sixty five of these isolates were typed to CC398 and a selection of these (n = 38) were further characterised for resistance and virulence genes, SCCmec and spa typing. Overall, MRSA was identified in 62/540 (11.5%) of environmental samples, 6/81 of the hand-plates (7.4%) and 13/208 of the SSIs (6.3%). spa t011 was the most frequent (24/38) and Based Upon Repeat Pattern (BURP) analysis identified spa t011 as one of the two group founders of the main spa CC identified across the five years (spa CC011/3423). However, 3 singletons (t073, t786, t064) were also identified suggesting separate introductions into the hospital environment. This long-term MRSA surveillance study revealed multiple introductions of MRSA CC398 in a UK Equine Hospital, identifying an emerging zoonotic pathogen so far only sporadically recorded in the UK.


Esthetics: a comparison of dentists' and patients' concepts.
Drawings and photographs of shape, symmetry, and proportion of maxillary central incisors were evaluated by 112 dentists, 215 dental sutdents, 399 male patients, and 695 female patients. A significant difference was found between the evaluations of patients and dentists; the preferences of dental student; were between those of patients and dentists. Male and female patients had similar opinions.


Synthesis of Phenylene Vinylene Macrocycles through Acyclic Diene Metathesis Macrocyclization and Their Aggregation Behavior.
A series of phenylene vinylene macrocycles (PVMs) bearing substituents with various sizes and electronic properties have been synthesized through a one-step acyclic diene metathesis macrocyclization approach and their aggregation behaviors have been investigated. In great contrast to the aggregation of the analogous phenylene ethynylene macrocycles, which aggregate only when substituted with electron-withdrawing groups, these PVMs undergo exceptionally strong aggregation, regardless of the electron-donating or -withdrawing characters of the substituents. The unusual aggregation behavior of the PVMs is further investigated with thermodynamic and computer modeling studies, which show a good agreement with the recently proposed direct through-space interaction model, rather than the polar/π model. The high aggregation tendency of PVMs suggests the great potential of this novel class of shape-persistent macrocycles in a variety of applications, such as ion channels, host-guest recognition, and catalysis.


Mechanisms of precise genome editing using oligonucleotide donors.
The use of programmable meganucleases is transforming genome editing and functional genomics. CRISPR/Cas9 was developed such that targeted genomic lesions could be introduced in vivo with unprecedented ease. In the presence of homology donors, these lesions facilitate high-efficiency precise genome editing (PGE) via homology-directed repair (HDR) pathways. However, the identity and hierarchy of the HDR (sub)pathways leading to the formation of PGE products remain elusive. Here, we established a green to blue fluorescent protein conversion system to systematically characterize oligodeoxynucleotide (ODN)-mediated PGE using Cas9 and its nickase variants in human cells. We demonstrate that, unlike double-stranded DNA (dsDNA) donors with central heterologies, ODNs generated short conversion tracts with Gaussian-like distributions. Interestingly, single-nick-induced PGE using ODN donors produced conversion tracts biased either mostly uni- or bidirectional depending on the relative strandedness of the ODNs and the nick. Moreover, the ODNs were physically incorporated into the genome only in the bidirectional, but not in the unidirectional, conversion pathway. In the presence of double-stranded genomic lesions, the unidirectional conversion pathway was preferentially utilized even though the knock-in mutation could theoretically have been converted by both pathways. Collectively, our results suggest that ODN-mediated PGE utilizes synthesis-dependent strand annealing and single-stranded DNA incorporation pathways. Both of these pathways generate short conversion tracts with Gaussian-like distributions. Although synthesis-dependent strand annealing is preferentially utilized, our work unequivocally establishes the existence of a single-stranded DNA incorporation pathway in human cells. This work extends the paradigms of HDR-mediated gene conversion and establishes guidelines for PGE in human cells.


Association of self-rated health with multimorbidity, chronic disease and psychosocial factors in a large middle-aged and older cohort from general practice: a cross-sectional study.
The prevalence of coexisting chronic conditions (multimorbidity) is rising. Disease labels, however, give little information about impact on subjective health and personal illness experience. We aim to examine the strength of association of single and multimorbid physical chronic diseases with self-rated health in a middle-aged and older population in England, and to determine whether any association is mediated by depression and other psychosocial factors. 25 268 individuals aged 39 to 79 years recruited from general practice registers in the European Prospective Investigation of Cancer (EPIC-Norfolk) study, completed a survey including self-rated health, psychosocial function and presence of common physical chronic conditions (cancer, stroke, heart attack, diabetes, asthma/bronchitis and arthritis). Logistic regression models determined odds of "moderate/poor" compared to "good/excellent" health by condition and number of conditions adjusting for psychosocial measures. One-third (8252) reported one, around 7.5% (1899) two, and around 1% (194) three or more conditions. Odds of "moderate/poor" self-rated health worsened with increasing number of conditions (one (OR = 1.3(1.2-1.4)) versus three or more (OR = 3.4(2.3-5.1)), and were highest where there was comorbidity with stroke (OR = 8.7(4.6-16.7)) or heart attack (OR = 8.5(5.3-13.6)). Psychosocial measures did not explain the association between chronic diseases and multimorbidity with self-rated health.The relationship of multimorbidity with self-rated health was particularly strong in men compared to women (three or more conditions: men (OR = 5.2(3.0-8.9)), women OR = 2.1(1.1-3.9)). Self-rated health provides a simple, integrative patient-centred assessment for evaluation of illness in the context of multiple chronic disease diagnoses. Those registering in general practice in particular men with three or more diseases or those with cardiovascular comorbidities and with poorer self-rated health may warrant further assessment and intervention to improve their physical and subjective health.


The nuclear hormone receptor NHR-86 controls anti-pathogen responses in C. elegans.
Nuclear hormone receptors (NHRs) are ligand-gated transcription factors that control adaptive host responses following recognition of specific endogenous or exogenous ligands. Although NHRs have expanded dramatically in C. elegans compared to other metazoans, the biological function of only a few of these genes has been characterized in detail. Here, we demonstrate that an NHR can activate an anti-pathogen transcriptional program. Using genetic epistasis experiments, transcriptome profiling analyses and chromatin immunoprecipitation-sequencing, we show that, in the presence of an immunostimulatory small molecule, NHR-86 binds to the promoters of immune effectors to activate their transcription. NHR-86 is not required for resistance to the bacterial pathogen Pseudomonas aeruginosa at baseline, but activation of NHR-86 by this compound drives a transcriptional program that provides protection against this pathogen. Interestingly, NHR-86 targets immune effectors whose basal regulation requires the canonical p38 MAPK PMK-1 immune pathway. However, NHR-86 functions independently of PMK-1 and modulates the transcription of these infection response genes directly. These findings characterize a new transcriptional regulator in C. elegans that can induce a protective host response towards a bacterial pathogen.


Kinetics of cardiac RyR channel gating studied at high temporal resolution.
Measurements of ryanodine receptor (RyR) activity during dynamic changes of calcium concentration have suggested that RyR has at least four calcium binding sites, and that activation transpires as an increase in the activity within the high open probability H-mode. Binding of several Ca2+ ions within the H-mode should manifest itself in the steady-state RyR activity by the presence of multiple closed times. However, previously only two closed times were detected in the H-mode of RyR activity. Here we recorded steady-state activity of single cardiac RyRs with high temporal resolution and compared it to data simulated under the same conditions using our previously published model of RyR gating. At a 10 kHz resolution, the closed time histograms of both experimental and simulated data had three exponential components. The closed times of simulated data were not significantly different from those obtained experimentally. After filtering at 2 kHz, only two exponential closed time components with time constants not significantly different from those previously published could be detected in both experimental and simulated records. The conformity of the steady-state experimental data to the model derived from the dynamic data provides further support for the idea that RyRs need binding of multiple Ca2+ ions to open.


Composition, roles, and regulation of cullin-based ubiquitin e3 ligases.
Due to their sessile nature, plants depend on flexible regulatory systems that allow them to adequately regulate developmental and physiological processes in context with environmental cues. The ubiquitin proteasome pathway, which targets a great number of proteins for degradation, is cellular tool that provides the necessary flexibility to accomplish this task. Ubiquitin E3 ligases provide the needed specificity to the pathway by selectively binding to particular substrates and facilitating their ubiquitylation. The largest group of E3 ligases known in plants is represented by CULLIN-REALLY INTERESTING NEW GENE (RING) E3 ligases (CRLs). In recent years, a great amount of knowledge has been generated to reveal the critical roles of these enzymes across all aspects of plant life. This review provides an overview of the different classes of CRLs in plants, their specific complex compositions, the variety of biological processes they control, and the regulatory steps that can affect their activities.


Does Considering the Consequences of Selective Exposure Help Reduce Selective Exposure Behaviors?
Selective exposure (the tendency to avoid information one disagrees with) is particularly easy to do and leads to problematic outcomes. This study investigated if personally relevant message frames would increase participant engagement and agreement when reading a counterattitudinal message. Participants (N = 180) were randomly assigned into one of three message frames: the idea attack frame asked participants to recall a time their ideas were attacked or summarily dismissed; the unable to defend position frame asked participants to recall a time they were vulnerable due to a lack of knowledge; and an irrelevant-frame control. Participants then read a counterattitudinal message about increasing internet service taxes. Next, participants rated their message agreement, and self-perceived engagement level. Although the messages did not influence agreement, the unable to defend position and the idea attack frames influenced participants to be more engaged with the message. This suggests that people are motivated to engage more with a counterattitudinal message when they are reminded of a time in which they were vulnerable due to a lack of knowledge or when others were summarily dismissive of their own ideas. Overall, both frames showed some promise and should be explored further.


Perspectives and prospects of chelation extraction of heavy metals from wastewater: A review.
Heavy metals' contamination of water resources is a global environmental issue due to their detrimental effects on human health. To safeguard humans and the environment, toxic heavy metals must be removed from contaminated water because they cannot be broken down. Diverse technologies are employed to reduce the levels of heavy metals in wastewater. However, these technologies suffer from being either costly or ineffective, particularly when the effluent has extremely low residual amounts. This review outlines the main accomplishments and promising future directions for solvent extraction as one of the potential methods of extracting heavy metals from water, utilizing literature reports. In addition to reviewing some of the commercial chelating reagents now in use, this article also discusses some of the obnoxious effects on human health that are associated with exposure to heavy metals.


Current practice in dialysis central venous catheter management: Multi-disciplinary renal team perspectives.
To explore the current practices related to the insertion, management and removal of dialysis central venous catheters (CVCs) used in patients with chronic kidney disease requiring haemodialysis. This qualitative descriptive study involved semi-structured interviews with surgeons, interventional radiologists, renal physicians, dialysis nurses, renal access nurses and renal researchers involved in the care of patients with chronic kidney disease requiring haemodialysis. Data were collected from staff at eight hospitals in six states and territories of Australia. Thirty-eight face-to-face interviews were conducted. A modified five-step qualitative content analysis approach was used to analyse the data. Improved visualization technology and its use by interventional radiologists has steered insertions to specialist teams in specialist locations. This is thought to have decreased risk and improved patient outcomes. Nurses were identified as the professional group responsible for maintaining catheter access integrity, preventing access failure and reducing access-related complications. While best practice was considered important, justifications for variations in practice related to local patient and environment challenges were identified. The interdisciplinary team is central in the insertion, maintenance, removal and education of patients regarding dialysis CVCs. Clinicians temper research-based decision-making about central dialysis access catheter management with knowledge of individual, environmental and patient factors. Strategies to ensure guidelines are appropriately translated for use in a wide variety of settings are necessary for patient safety.


Effects of Diallyl Trisulfide, an Active Substance from Garlic Essential Oil, on Energy Metabolism in Male Moth Sitotroga cerealella (Olivier).
This study investigated the effects of diallyl trisulfide (DAT), an active substance from garlic essential oil, on the metabolism of the main energy substances of pre- and postmating males of Sitotroga cerealella. Males at 12 h postemergence were fumigated with DAT at a concentration (LC10 = 0.010 µL/L) in a glass jar for 7 h. The main energy metabolites from pre- and postmating males were determined, including protein, triglyceride, glycogen, total soluble sugar, trehalose, and trehalase. The contents of total protein and total soluble sugar and the trehalase activity of premating males were significantly increased following DAT treatment, whereas the contents of protein from the accessory gland, triglyceride, glycogen, and trehalose were significantly decreased after treatment. Additionally, after mating, the total protein and soluble sugar contents were significantly increased and the glycogen content was significantly decreased in the treatment group relative to the levels in controls, but there was no significant difference observed in triglyceride, accessory gland proteins, trehalose content, or trehalase activity between the treatment and control groups. Furthermore, the changes in the main energy substances between pre- and postmating in males after the DAT treatment (∆DAT) were smaller than those in the control group (∆CK). This result indicated that DAT can accelerate the rate of metabolism in males at LC10, leading to the accumulation of greater levels of total soluble sugar to support life activities and to the increased synthesis of proteins to resist an adverse environment.


Psychosocial crisis intervention for coronavirus disease 2019 patients and healthcare workers.
Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.


AE-941 (AEterna).
AEterna is developing AE-941, an angiogenesis inhibitor derived from the ultrafiltration of liquid shark cartilage, with matrix metalloprotease (MMP)-2, MMP-9 and vascular endothelial growth factor inhibitory properties, for the potential treatment of non-small-cell lung cancer.


Comparison of Adaptive Spectral Estimation for Vehicle Speed Measurement with Radar Sensors.
Vehicle speed-over-ground (SoG) radar offers significant advantages over conventional speed measurement systems. Radar sensors enable contactless speed measurement, which is free from wheel slip. One of the key issues in SoG radar is the development of the Doppler shift estimation algorithm. In this paper, we compared two algorithms to estimate a mean Doppler frequency accurately. The first is the center-of-mass algorithm, which based on spectrum center-of-mass estimation with a bandwidth-limiting technique. The second is the cross-correlation algorithm, which is based on a cross-correlation technique by cross-correlating Doppler spectrum with a theoretical Gaussian curve. Analysis shows that both algorithms are computationally efficient and suitable for real-time SoG systems. Our extensive simulated and experimental results show both methods achieved low estimation error between 0.5% and 1.5% for flat road conditions. In terms of reliability, the cross-correlation method shows good performance under low Signal-to-Noise Ratio (SNR) while the center-of-mass method failed in this condition.


Clinical manifestations of obstructive sleep apnoea in pregnancy: more than snoring and witnessed apnoeas.
Sleep disordered breathing and its symptoms have been associated with a multitude of fetal and maternal complications including gestational hypertensive disorders, gestational diabetes and possibly pre-term labour and other markers of alterations in fetal wellbeing. The disease remains underdiagnosed in the general population but likely also in pregnancy, mostly because providers do not appropriately screen for the disorder. Sleep disordered breathing may manifest differently in women, since women report more fatigue and less snoring than men do. This paper discusses typical presentations of sleep disordered breathing but also reports some less obvious presentations to help providers recognise those manifestations and screen for the disorder when warranted. Our case series describes patients with diagnoses such as chronic hypertension, pre-eclampsia, pulmonary hypertension, nocturnal asthma and panic attacks, who were diagnosed with sleep disordered breathing and offered treatment with CPAP during pregnancy.


Clinical and histological characteristics of chronic hepatitis B with negative hepatitis B e-antigen.
To study the clinical and histological features of chronic hepatitis B (CHB) with negative hepatitis B e-antigen (HBeAg). A total of 743 in-patients with chronic hepatitis B were recruited into the study and divided into two groups according to the HBeAg status. The correlation among alanine transaminase (ALT) levels, hepatitis B virus (HBV) DNA semiquantification, and the liver histopathological data were detected. Of the 743 successive in-patients, 267 (35.9%) were HBeAg-negative. The HBDAG-negative group had significantly lower serologic HBV DNA levels (63.0% of < 100 pg/ml) vs HBeAg-positive (42.6%, P < 0.001), while more sever inflammation (58.1% of inflammatory scores of histological activity index (HAIinf > or = 9) vs HBeAg-positive group (46.0%, P < 0.001) and severe fibrosis (45.3% of fibrosis scores of histological activity index (HAIfib > or = 3) vs HBeAg-positive group (27.9%, P < 0.001) of liver histology. In HBeAg-positive patients, increasing ALI levels were significantly associated with high inflammation and fibrosis scores and low HBV DNA levels. However, it was not the case in the HBeAg-negative cases. In HBeAg-positive patients, 91.3% of them had HAIinf > or = 9 and 65.7% had HAIfib > or = 3 with HBV DNA > 100 pg/ml, while 8.2% of them had HAIinf > or = 9 and 12.3% had HAIfib > or = 3 with HBV DNA < 20 pg/ml, indicating an obverse correlation between HBV DNA levels and histology scores. As regards clinical and histological background, the chronic HBeAg-negative hepatitis B is a different subpopulation from the HBeAg-positive counterpart.


Paget disease of the humerus mimicking metastatic disease in a patient with metastatic malignant mesothelioma on whole body F-18 FDG PET/CT.
A 71-year-old man with newly diagnosed malignant mesothelioma was referred for an F-18 FDG PET/CT study to evaluate the extent of disease. PET showed mild FDG uptake in the right chest, corresponding to a lobulated, mass-like right pleural effusion versus thickening involving the entire right pleural space, and some mediastinal involvement, on the accompanying CT scan. In addition, marked FDG uptake was seen in the proximal left humerus, suspicious for an osseous metastasis. The corresponding CT scan findings of cortical thickening and a "Swiss cheese" appearance were most consistent with Paget disease. The intense FDG uptake in an osseous lesion on FDG-PET in our case reminds us of the variable nature of FDG uptake in Paget disease, the possibility of false-positive findings on FDG-PET in patients with cancer, and the usefulness of the fusion techniques in the evaluation of skeletal lesions, with the potential for discriminating between benign Paget disease and other pathologic bone findings.


The potential impact of novel investigational compounds on human fertility.
There is considerable concern that the incidence of infertility in humans may be increasing, in some instances due to the action of bioactive xenobiotic compounds found in our environment; for example, high concentrations of xenobiotics with estrogenic activity can interfere with normal testicular function and fertility. However, recent studies have shown that very low concentrations of several estrogenic xenobiotics can have subtle, unexpected effects on sperm function. When tested in vitro, these compounds stimulate spermatozoa to become fertile very quickly, but continued stimulation causes them to burn out and lose fertilising ability; similar responses occurring in vivo could reduce fertility. In contrast, several other compounds, structurally related to amfetamine, have been shown to act on spermatozoa in vitro in a positive manner, stimulating cells to 'switch on' quickly and then preventing burnout so that they maintain fertilising potential; similar responses occurring in vivo could enhance fertility. These results could have implications for either reducing or enhancing natural fertility.


Blood cyclosporine pharmacokinetics in patients undergoing marrow transplantation. Influence of age, obesity, and hematocrit.
Blood cyclosporine pharmacokinetics were studied in 85 patients aged 1-52 (median: 22) years undergoing allogeneic bone marrow transplantation for the treatment of hematologic disease. Pharmacokinetic studies were carried out during the first two weeks posttransplant after an intravenous dose of 2.1-4.4 mg/kg. Whole-blood cyclosporine concentrations were measured by high-performance liquid chromatography. Multiple stepwise regression analysis indicated that age (P less than 0.001) and hematocrit (P less than 0.05) correlated with cyclosporine clearance (CL) while steady-state volume of distribution (Vss) did not correlate with any of the factors studied. Cyclosporine CL significantly differed among nonobese patients in different age groups; patients less than or equal to 10 years old had a higher mean CL (13.1 ml/min/kg) than patients 11-20, 21-30, 31-40, or greater than 40 years old (mean CL: 8.5-10.3 ml/min/kg) (P less than 0.05). No significant differences in cyclosporine CL and Vss were observed between obese (greater than 125% ideal body weight) patients and age-matched nonobese patients. Hematocrit values (range: 24-39) were inversely correlated with cyclosporine CL, which suggests that red blood cells function as important ligands in cyclosporine binding. These results show that blood cyclosporine CL is higher in marrow transplant recipients than in solid organ transplant recipients and that these differences may be related to lower hematocrits in marrow transplant recipients compared with solid organ transplant recipients. When compared with previously published serum cyclosporine CL data, our findings suggest that age-related changes in CL are primarily related to changes in plasma protein binding and that obesity does not significantly alter cyclosporine CL and Vss.


Attitude of Jordanian Nursing Educators Toward Integration of Disaster Management in Nursing Curricula.
Nursing education plays a significant role in preparing nurses for disasters; it helps in increasing their knowledge about disasters. The purpose of this study was to explore the attitude of nursing educators in Jordan toward the integration of disaster preparedness contents in nursing curricula. A descriptive cross-sectional survey was used. The instrument comprises 51 Likert-scale items; 150 questionnaires were distributed to nursing educators in all of the private and government universities. Data were analyzed using the Statistical Package for Social Science (SPSS), version 22 (IBM Corp, Armonk, NY). One hundred thirty-one (131) results were collected with an 87% response rate. All participants perceived that the integration of a disaster course in nursing curricula is quite important. Findings indicated a lack of nursing educators' life experiences regarding disaster management. No significant differences were found in terms of age, area of experience, or years of teaching. Incorporating disaster management courses into nursing curricula will help resolve the lack of knowledge. Nursing educators have a low level of knowledge in disaster management. This highlights the necessity for preparing nursing educators for disasters by encouraging their participation in disaster management training. Therefore, they will circulate this information adequately to students accordingly.


Surface-Functionalized Polymeric siRNA Nanoparticles for Tunable Targeting and Intracellular Delivery to Hematologic Cancer Cells.
To date, the application of RNA therapeutics to hematologic malignancies has been challenging owing to the resistance of blood cancer cells against conventional transfection methods. Herein, triple-targeting moiety-functionalized polymeric small interfering RNA (siRNA) nanoparticles were systematically developed for efficient targeted delivery of RNA therapeutics to hematologic cancer cells. Polymeric siRNAs were synthesized using rolling circle transcription and were surface-functionalized with three types of targeting moieties─a natural ligand and two additional combinations of cell-specific antibodies─for tunable targetability. As a proof of concept, the optimization of the hyaluronic acid/antibody conjugation ratio was performed for selective intracellular delivery to various non-Hodgkin's lymphoma (NHL) cell lines (Daudi, Raji, Ramos, and Toledo cells) via receptor-mediated endocytosis. The engineered nanoparticles showed almost 10-fold enhanced NHL-specific intracellular delivery and induced significant in vitro anticancer effects. This multitargeted nanoparticle platform may effectively support the intracellular delivery of polymeric siRNA sequences, and thus promote therapeutic effects in hematopoietic malignancies.


Preliminary Comparison of Oral and Intestinal Human Microbiota in Patients with Colorectal Cancer: A Pilot Study.
In this study Next-Generation Sequencing (NGS) was used to analyze and compare human microbiota from three different compartments, i.e., saliva, feces, and cancer tissue (CT), of a selected cohort of 10 Italian patients with colorectal cancer (CRC) vs. 10 healthy controls (saliva and feces). Furthermore, the Fusobacterium nucleatum abundance in the same body site was investigated through real-time quantitative polymerase chain reaction (qPCR) to assess the association with CRC. Differences in bacterial composition, F. nucleatum abundance in healthy controls vs. CRC patients, and the association of F. nucleatum with clinical parameters were observed. Taxonomic analysis based on 16S rRNA gene, revealed the presence of three main bacterial phyla, which includes about 80% of reads: Firmicutes (39.18%), Bacteroidetes (30.36%), and Proteobacteria (10.65%). The results highlighted the presence of different bacterial compositions; in particular, the fecal samples of CRC patients seemed to be enriched with Bacteroidetes, whereas in the fecal samples of healthy controls Firmicutes were one of the major phyla detected though these differences were not statistically significant. The CT samples showed the highest alpha diversity values. These results emphasize a different taxonomic composition of feces from CRC compared to healthy controls. Despite the low number of samples included in the study, these results suggest the importance of microbiota in the CRC progression and could pave the way to the development of therapeutic interventions and novel microbial-related diagnostic tools in CRC patients.


Autophagy Plays Prominent Roles in Amino Acid, Nucleotide, and Carbohydrate Metabolism during Fixed-Carbon Starvation in Maize.
Autophagic recycling of proteins, lipids, nucleic acids, carbohydrates, and organelles is essential for cellular homeostasis and optimal health, especially under nutrient-limiting conditions. To better understand how this turnover affects plant growth, development, and survival upon nutrient stress, we applied an integrated multiomics approach to study maize (Zea mays) autophagy mutants subjected to fixed-carbon starvation induced by darkness. Broad metabolic alterations were evident in leaves missing the core autophagy component ATG12 under normal growth conditions (e.g., lipids and secondary metabolism), while changes in amino acid-, carbohydrate-, and nucleotide-related metabolites selectively emerged during fixed-carbon starvation. Through combined proteomic and transcriptomic analyses, we identified numerous autophagy-responsive proteins, which revealed processes underpinning the various metabolic changes seen during carbon stress as well as potential autophagic cargo. Strikingly, a strong upregulation of various catabolic processes was observed in the absence of autophagy, including increases in simple carbohydrate levels with a commensurate drop in starch levels, elevated free amino acid levels with a corresponding reduction in intact protein levels, and a strong increase in the abundance of several nitrogen-rich nucleotide catabolites. Altogether, this analysis showed that fixed-carbon starvation in the absence of autophagy adjusts the choice of respiratory substrates, promotes the transition of peroxisomes to glyoxysomes, and enhances the retention of assimilated nitrogen.


[Association of GPER gene polymorphism with social function of children with attention deficit hyperactivity disorder].
To assess the association of G protein-coupled estrogen receptor(GPER) gene polymorphism with social function of children with attention deficit hyperactivity disorder (ADHD). The social function of 135 children with ADHD were assessed by Weiss Functional Impairment Scale-Parent form (WFIRS-P). The coding region of GPER gene of all patients was subjected to Sanger sequencing. The association of polymorphisms with the social function of the ADHD children was analyzed. In the case group, the social function scores of Learning and School and Risky Activities of boys were significantly higher than those of girls (t=2.704, P=0.008; t=2.289, P=0.027). No significant difference was found in the genotypic frequencies of the c.-9T/C and c.789G/A loci between different genders. But the learning and school scores of those with a TC genotype for the c.-9T to C locus were significantly higher than those with a TT genotype (t= 2.159, P=0.033). For children with ADHD, the social function of Learning and School of those with a TC genotype of the GPER gene c.-9T/C locus is more severely damaged compared with those with a TT genotype.


Dietary conjugated linoleic acid enhances spleen PPAR-gamma mRNA expression in broiler chicks.
1. The anti-inflammatory effects of dietary conjugated linoleic acid (CLA) on broilers repeatedly challenged with lipopolysaccharide (LPS) were investigated. 2. Day-old broiler chicks were allotted into three treatment groups and fed on a control diet or diets containing 5.0 or 10.0 g CLA/kg diet. Six chicks from each treatment were injected with LPS (0.25 mg/kg body weight) at 16, 18 and 20 d of age. Splenic cyclooxygenase (COX) and inducible nitric oxide synthase (iNOS) activities, and prostaglandin E(2) (PGE(2)) and nitric oxide (NO) production as well as peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA expression were measured at 21 d of age. 3. Chicks fed 10.0 g CLA/kg diet had lower COX activities and PGE(2) production that the controls. Dietary CLA (10.0 g/kg) did not significantly diminish LPS-induced enhancement of COS-2 activity, inhibited the subsequent increase in PGE(2) production. 4. Regulation of COX-1 activity contributed to the difference in PGE(2) production. 5. CLA did not markedly attenuate the increase of iNOS activity and NO production caused by LPS challenge. Chicks fed CLA had lower iNOS activity and NO production than the controls. 6. Dietary CLA activated splenic PPAR-gamma mRNA expression and increased PPAR-gamma mRNA expression after LPS injection. 7. These results suggest that dietary CLA has immunomodulatory effects in the spleen by restricting basal PGE(2) and NO to lower levels and enhancing PPAR-gamma mRNA expression. During the inflammatory response, dietary CLA did not alleviate the increase in COX-2 and iNOS activities but enhanced PPAT-gamma mRNA expression.


Revisiting the genus Photobacterium: taxonomy, ecology and pathogenesis.
The genus Photobacterium, one of the eight genera included in the family Vibrionaceae, contains 27 species with valid names and it has received attention because of the bioluminescence and pathogenesis mechanisms that some of its species exhibit. However, the taxonomy and phylogeny of this genus are not completely elucidated; for example, P. logei and P. fischeri are now considered members of the genus Aliivibrio, and previously were included in the genus Vibrio. In addition, P. damselae subsp. piscicida was formed as a new combination for former Vibrio damsela and Pasteurella piscicida. Moreover, P. damselae subsp. damselae is an earlier heterotypic synonym of P. histaminum. To avoid these incovenences draft and complete genomic sequences of members of Photobacterium are increasingly becoming available and their use is now routine for many research laboratories to address diverse goals: species delineation with overall genomic indexes, phylogenetic analyses, comparative genomics, and phenotypic inference. The habitats and isolation source of the Photobacterium species include seawater, sea sediments, saline lake waters, and a variety of marine organisms with which the photobacteria establish different relationships, from symbiosis to pathogenic interactions. Several species of this genus contain bioluminescent strains in symbiosis with marine fish and cephalopods; in addition, other species enhance its growth at pressures above 1 atmosphere, by means of several high-pressure adaptation mechanisms and for this, they may be considered as piezophilic (former barophilic) bacteria. Until now, only P. jeanii, P. rosenbergii, P. sanctipauli, and the two subspecies of P. damselae have been reported as responsible agents of several pathologies on animal hosts, such as corals, sponges, fish and homeothermic animals. In this review we have revised and updated the taxonomy, ecology and pathogenicity of several members of this genus. [Int Microbiol 20(1): 1-10 (2017)].


Interdigitation of contralateral and ipsilateral columnar projections to frontal association cortex in primates.
The combined use of two anterograde axonal transport methods reveals that in the prefrontal association cortex of macaque monkeys, associational projections from the parietal lobe of one hemisphere interdigitate with callosal projections from the opposite frontal lobe, forming adjacent columns 300 to 750 micrometers wide. The finding of separate and alternating ipsilateral and contralateral inputs in the frontal association cortex opens up new possibilities for the functional analysis of this large but unexplored area of the primate brain.


Neglected filoviruses.
Eight viruses are currently assigned to the family Filoviridae Marburg virus, Sudan virus and, in particular, Ebola virus have received the most attention both by researchers and the public from 1967 to 2013. During this period, natural human filovirus disease outbreaks occurred sporadically in Equatorial Africa and, despite high case-fatality rates, never included more than several dozen to a few hundred infections per outbreak. Research emphasis shifted almost exclusively to Ebola virus in 2014, when this virus was identified as the cause of an outbreak that has thus far involved more than 28 646 people and caused more than 11 323 deaths in Western Africa. Consequently, major efforts are currently underway to develop licensed medical countermeasures against Ebola virus infection. However, the ecology of and mechanisms behind Ebola virus emergence are as little understood as they are for all other filoviruses. Consequently, the possibility of the future occurrence of a large disease outbreak caused by other less characterized filoviruses (i.e. Bundibugyo virus, Lloviu virus, Ravn virus, Reston virus and Taï Forest virus) is impossible to rule out. Yet, for many of these viruses, not even rudimentary research tools are available, let alone medical countermeasures. This review summarizes the current knowledge on these less well-characterized filoviruses.


A NAP-AAO3 regulatory module promotes chlorophyll degradation via ABA biosynthesis in Arabidopsis leaves.
Chlorophyll degradation is an important part of leaf senescence, but the underlying regulatory mechanisms are largely unknown. Excised leaves of an Arabidopsis thaliana NAC-LIKE, ACTIVATED BY AP3/PI (NAP) transcription factor mutant (nap) exhibited lower transcript levels of known chlorophyll degradation genes, STAY-GREEN1 (SGR1), NON-YELLOW COLORING1 (NYC1), PHEOPHYTINASE (PPH), and PHEIDE a OXYGENASE (PaO), and higher chlorophyll retention than the wild type during dark-induced senescence. Transcriptome coexpression analysis revealed that abscisic acid (ABA) metabolism/signaling genes were disproportionately represented among those positively correlated with NAP expression. ABA levels were abnormally low in nap leaves during extended darkness. The ABA biosynthetic genes 9-CIS-EPOXYCAROTENOID DIOXYGENASE2, ABA DEFICIENT3, and ABSCISIC ALDEHYDE OXIDASE3 (AAO3) exhibited abnormally low transcript levels in dark-treated nap leaves. NAP transactivated the promoter of AAO3 in mesophyll cell protoplasts, and electrophoretic mobility shift assays showed that NAP can bind directly to a segment (-196 to -162 relative to the ATG start codon) of the AAO3 promoter. Exogenous application of ABA increased the transcript levels of SGR1, NYC1, PPH, and PaO and suppressed the stay-green phenotype of nap leaves during extended darkness. Overexpression of AAO3 in nap leaves also suppressed the stay-green phenotype under extended darkness. Collectively, the results show that NAP promotes chlorophyll degradation by enhancing transcription of AAO3, which leads to increased levels of the senescence-inducing hormone ABA.


Ventral lateral geniculate nucleus projects to the dorsal lateral geniculate nucleus in the cat.
The lamina C3 of the dorsal lateral geniculate nucleus of the cat does not receive retinal projections but instead receives visual information from the small subpopulation of W-type ganglion cells via the upper substratum of the stratum griseum superficiale of the superior colliculus. We herein report a projection from the lateral division of the ventral lateral geniculate nucleus into the lamina C3 of the dorsal lateral geniculate nucleus. As the lateral division receives projections from the contralateral retina and the ipsilateral upper stratum griseum superficiale of the superior colliculus, we suggest that these regions make up a small cell type W-cell neuronal network that provides visual information to layer I of the striate cortex via the lamina C3.


Robust tracking and quantification of C. elegans body shape and locomotion through coiling, entanglement, and omega bends.
The behavior of the well-characterized nematode, Caenorhabditis elegans (C. elegans), is often used to study the neurologic control of sensory and motor systems in models of health and neurodegenerative disease. To advance the quantification of behaviors to match the progress made in the breakthroughs of genetics, RNA, proteins, and neuronal circuitry, analysis must be able to extract subtle changes in worm locomotion across a population. The analysis of worm crawling motion is complex due to self-overlap, coiling, and entanglement. Using current techniques, the scope of the analysis is typically restricted to worms to their non-occluded, uncoiled state which is incomplete and fundamentally biased. Using a model describing the worm shape and crawling motion, we designed a deformable shape estimation algorithm that is robust to coiling and entanglement. This model-based shape estimation algorithm has been incorporated into a framework where multiple worms can be automatically detected and tracked simultaneously throughout the entire video sequence, thereby increasing throughput as well as data validity. The newly developed algorithms were validated against 10 manually labeled datasets obtained from video sequences comprised of various image resolutions and video frame rates. The data presented demonstrate that tracking methods incorporated in WormLab enable stable and accurate detection of these worms through coiling and entanglement. Such challenging tracking scenarios are common occurrences during normal worm locomotion. The ability for the described approach to provide stable and accurate detection of C. elegans is critical to achieve unbiased locomotory analysis of worm motion.