Metal-Organic Framework MIL-101-NH2-Supported Acetate-Based Butylimidazolium Ionic Liquid as a Highly Efficient Heterogeneous Catalyst for the Synthesis of 3-Aryl-2-oxazolidinones.

A novel heterogeneous catalyst, the ionic liquid (IL) of 1-butyl-3-methylimidazolium acetate (BmimOAc) immobilized on MIL-101-NH2, denoted as IL(OAc-)-MIL-101-NH2, was prepared by the "ship-in-a-bottle" strategy. The IL of BmimOAc was prepared in the MIL-101-NH2 nanocages primordially, in which the condensation product of MIL-101-NH2's amine group with 1,1'-carbonyldiimidazole (CDI) reacted with 1-bromo butane, and then the intermediate exchanged with potassium acetate. The structure and physicochemical properties of IL(OAc-)-MIL-101-NH2 were characterized by powder X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, DRS UV-vis, nitrogen adsorption-desorption, and elemental analysis. The results indicated that BmimOAc was anchored in the MIL-101-NH2 skeleton via the acylamino group and confined in the nanocages in the form of a single molecule. The composite material of IL(OAc-)-MIL-101-NH2 exhibited excellent catalytic activity and catalytically synthesized 3-aryl-2-oxazolone in an excellent yield of 92%. It can be reused up to six times without noteworthy loss of its activity and demonstrated distinct size-selective property for substrates. It was conjectured that the diffusion kinetics of reactants could be controlled by the aperture size of the metal-organic framework support.

Genetic insights on sleep schedules: this time, it's PERsonal.

The study of circadian rhythms is emerging as a fruitful opportunity for understanding cellular mechanisms that govern human physiology and behavior, fueled by evidence directly linking sleep disorders to genetic mutations affecting circadian molecular pathways. Familial advanced sleep-phase disorder (FASPD) is the first recognized Mendelian circadian rhythm trait, and affected individuals exhibit exceptionally early sleep-wake onset due to altered post-translational regulation of period homolog 2 (PER2). Behavioral and cellular circadian rhythms are analogously affected because the circadian period length of behavior is reduced in the absence of environmental time cues, and cycle duration of the molecular clock is likewise shortened. In light of these findings, we review the PER2 dynamics in the context of circadian regulation to reveal the mechanism of sleep-schedule modulation. Understanding PER2 regulation and functionality may shed new light on how our genetic composition can influence our sleep-wake behaviors.

A culture system to study oligodendrocyte myelination processes using engineered nanofibers.

Current methods for studying central nervous system myelination necessitate permissive axonal substrates conducive to myelin wrapping by oligodendrocytes. We have developed a neuron-free culture system in which electron-spun nanofibers of varying sizes substitute for axons as a substrate for oligodendrocyte myelination, thereby allowing manipulation of the biophysical elements of axonal-oligodendroglial interactions. To investigate axonal regulation of myelination, this system effectively uncouples the role of molecular (inductive) cues from that of biophysical properties of the axon. We use this method to uncover the causation and sufficiency of fiber diameter in the initiation of concentric wrapping by rat oligodendrocytes. We also show that oligodendrocyte precursor cells display sensitivity to the biophysical properties of fiber diameter and initiate membrane ensheathment before differentiation. The use of nanofiber scaffolds will enable screening for potential therapeutic agents that promote oligodendrocyte differentiation and myelination and will also provide valuable insight into the processes involved in remyelination.

Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination.

A requisite component of nervous system development is the achievement of cellular recognition and spatial segregation through competition-based refinement mechanisms. Competition for available axon space by myelinating oligodendrocytes ensures that all relevant CNS axons are myelinated properly. To ascertain the nature of this competition, we generated a transgenic mouse with sparsely labeled oligodendrocytes and establish that individual oligodendrocytes occupying similar axon tracts can greatly vary the number and lengths of their myelin internodes. Here we show that intercellular interactions between competing oligodendroglia influence the number and length of myelin internodes, referred to as myelinogenic potential, and identify the amino-terminal region of Nogo-A, expressed by oligodendroglia, as necessary and sufficient to inhibit this process. Exuberant and expansive myelination/remyelination is detected in the absence of Nogo during development and after demyelination, suggesting that spatial segregation and myelin extent is limited by microenvironmental inhibition. We demonstrate a unique physiological role for Nogo-A in the precise myelination of the developing CNS. Maximizing the myelinogenic potential of oligodendrocytes may offer an effective strategy for repair in future therapies for demyelination.

What Do Mothers know about Neonatal Jaundice? Knowledge, Attitude and Practice of Mothers in Malaysia.

No abstract available.

An unusual presentation of lymphoma of the head and neck region.

A 33-year-old Malay lady presented to us with 1-month history of globus sensation in the throat. Clinically, she had a 3cmx2cmx1cm sessile soft mass arising from the right tongue base and was treated as hypertrophied lingual tonsil. Biopsy of the mass was done when the patient developed bleeding and was reported as diffuse non-Hodgkin's B-cell lymphoma. Globus sensation is a common complaint in the ORL clinic. It is important to be able to decide if further investigation is warranted to differentiate a malignant from a benign lesion as at times, a malignant lesion can masquerade as a harmless lesion.

A Rare Mutation of ß1-Adrenergic Receptor Affects Sleep/Wake Behaviors.

Sleep is crucial for our survival, and many diseases are linked to long-term poor sleep quality. Before we can use sleep to enhance our health and performance and alleviate diseases associated with poor sleep, a greater understanding of sleep regulation is necessary. We have identified a mutation in the ß1-adrenergic receptor gene in humans who require fewer hours of sleep than most. In vitro, this mutation leads to decreased protein stability and dampened signaling in response to agonist treatment. In vivo, the mice carrying the same mutation demonstrated short sleep behavior. We found that this receptor is highly expressed in the dorsal pons and that these ADRB1+ neurons are active during rapid eye movement (REM) sleep and wakefulness. Activating these neurons can lead to wakefulness, and the activity of these neurons is affected by the mutation. These results highlight the important role of ß1-adrenergic receptors in sleep/wake regulation.

Disorders of sleep and circadian rhythms.

Sleep is fundamental to the survival of humans. However, knowledge regarding the role of sleep and its regulation is poorly understood. Genetics in flies, mice, and humans has led to a detailed understanding of some aspects of circadian regulation. Sleep homeostasis (the effect of increasing periods of wakefulness on our sleep propensity) is largely not understood. Sleep homeostasis is distinct from, but also linked to, the circadian clock. It is only in the last two decades that our understanding of some sleep disorders has been revealed. These breakthroughs were mostly fueled by intensive investigation using genetic tools. Although modern human genetics has revolutionized scientific research of neurologic disorders beginning ~35 years ago, studies of sleep and sleep disorders have lagged behind those of many neurologic diseases. This is due to the complexity in phenotyping behaviors like sleep and the fact that sleep is strongly influenced by environmental and other factors. We have long been aware that the amount of sleep required by individuals is normally distributed in the general population with small proportions of people being natural short or natural long sleepers. However, it has been less than a decade since Mendelian families of natural short sleepers have been recognized. Recent work has made significant advances and mechanistic insights of several sleep disorders as well as familial natural short sleepers by using ever-improving human genetic and cellular molecular tools. Given recent advances into genetic and biologic understanding of sleep, the hope of understanding this indispensable process is closer. Ultimately, our growing understanding will lead to more effective treatments of human sleep disorders.

Physicochemical properties of pectin from green jelly leaf (Cyclea barbata Miers).

The water extract of Green Jelly leaves (GJL) obtained by crushing the leaves in water (1:40) was capable of forming a gel at room temperature. The composition of GJL consisted mainly of carbohydrate (∼70w/w), protein (∼13% w/w) and minerals (∼6% w/w). The mineral portion consisted of mainly calcium (∼1.2% w/w), zinc (∼0.12% w/w) and magnesium (∼0.11% w/w). The isolated polysaccharide fraction (∼42.6% w/w) consisted of mainly galacturonic acid (∼35.8% w/w) and neutral sugars (∼6.8% w/w), with a weight-average molecular weight of ∼4.4×105g/mol. The results obtained by Fourier Transform Infra-Red (FTIR) showed that GJL polysaccharide fraction had a fairly similar FTIR fingerprint as the commercial low-methoxyl pectin (LMP). The degree of esterification of the polysaccharide changed drastically (from 97% to 10%) depending on the temperature used during the extraction process. The zeta potential of the extracted polysaccharide showed high negative charged as compared to the commercial LMP but close to sodium alginate. The study showed that the gelation was divalent cation-mediated and probably facilitated by the low degree of esterification which reduced steric hindrance from the methyl ester groups.

Chirality as a tool for function in porous organic cages.

The control of solid state assembly for porous organic cages is more challenging than for extended frameworks, such as metal-organic frameworks. Chiral recognition is one approach to achieving this control. Here we investigate chiral analogues of cages that were previously studied as racemates. We show that chiral cages can be produced directly from chiral precursors or by separating racemic cages by co-crystallisation with a second chiral cage, opening up a route to producing chiral cages from achiral precursors. These chiral cages can be cocrystallized in a modular, 'isoreticular' fashion, thus modifying porosity, although some chiral pairings require a specific solvent to direct the crystal into the desired packing mode. Certain cages are shown to interconvert chirality in solution, and the steric factors governing this behavior are explored both by experiment and by computational modelling.

Reticular synthesis of porous molecular 1D nanotubes and 3D networks.

Synthetic control over pore size and pore connectivity is the crowning achievement for porous metal-organic frameworks (MOFs). The same level of control has not been achieved for molecular crystals, which are not defined by strong, directional intermolecular coordination bonds. Hence, molecular crystallization is inherently less controllable than framework crystallization, and there are fewer examples of 'reticular synthesis', in which multiple building blocks can be assembled according to a common assembly motif. Here we apply a chiral recognition strategy to a new family of tubular covalent cages to create both 1D porous nanotubes and 3D diamondoid pillared porous networks. The diamondoid networks are analogous to MOFs prepared from tetrahedral metal nodes and linear ditopic organic linkers. The crystal structures can be rationalized by computational lattice-energy searches, which provide an in silico screening method to evaluate candidate molecular building blocks. These results are a blueprint for applying the 'node and strut' principles of reticular synthesis to molecular crystals.

Predictors of general discomfort, limitations in activities of daily living and intention of a second donation in unrelated hematopoietic stem cell donation.

We performed a retrospective study of 1868 consecutive unrelated donors to predict the risk factors related to general discomfort, limitations in activities of daily living (ADLs) and intention of a second donation in hematopoietic stem cell (HSC) donation. General discomfort and limitations in ADLs were assessed by numerical measurement (scores of 0-10) and donor's intention of a second donation by yes or no reply. The post-donation questionnaires were completed within 48 h after HSC collection and at 1 week, 4 weeks, and 4 months thereafter. Predictors of general discomfort included female sex (P<0.0001), bone marrow (BM) collection (P<0.0001) or PBSC collection through a central line (CL; P=0.0349), 2-day collection (P=0.0150) and negative or undetermined intention of a second donation on day 1 (P<0.0001). Predictors of limitations in ADLs included age group of 30-39 years (P=0.0046), female sex (P<0.0001), BM collection (P<0.0001) or PBSC collection through a CL (P<0.0001) and negative or undetermined intention of a second donation on day 1 (P<0.0001). The only predictor of positive intention of a second donation was male sex (P=0.0007). Age, sex and collection method and period should be considered risk factors when unrelated HSC donation is performed.

Tubulovesicular elements in Blastocystis hominis from the caecum of experimentally-infected rats.

By transmission electron microscopy (TEM), tubulovesicular elements were seen in Blastocystis hominis obtained from the caecum of experimentally-infected rats. These appeared to arise from the peripheral cytoplasm and were rounded, oval or elongate in sections. It is suggested that these elements form a network for transfer of nutrients to the periphery during the process of encystation.

The correlation of telomerase and IL-10 with leukemia transformation in a mouse model of chronic lymphocytic leukemia (CLL).

Telomerase activity is upregulated in activated and malignant lymphocytes. We studied the correlation of telomerase and IL-10 to leukemia transformation in the NZB mouse model of human chronic lymphocytic leukemia (CLL). Telomerase levels increased from early to late leukemic stages, likewise IL-10 gene expression levels increased with the leukemic progression. The inverse relationship of telomerase and IL-10 levels to the survival of NZB mice was also established. Our data suggested that telomerase and IL-10 were involved in transformation in the murine model of CLL and the detection of telomerase activities might be of value in the prediction of CLL progression.

Difference in the expression of Fas/Fas-ligand and the lymphocyte subset reconstitution according to the occurrence of acute GVHD.

Acute graft-versus-host disease (aGVHD) remains a major barrier to a wider application of allogeneic bone marrow transplantation (BMT). Although this complication is mainly dependent on donor-derived T lymphocytes, very little information is available concerning the mechanism of lethality. In this study, we investigated both the expression of Fas/Fas-ligand (FasL) and lymphocyte subset reconstitution in patients who underwent HLA-matched related allogeneic BMT (n = 16) and normal donors (n = 10), and several distinct features were observed. First, the reconstitutions of CD3+ and CD56+ cells were different between the aGVHD+ and aGVHD- group. In particular, the percentage of CD3-CD56+ cells was significantly decreased in patients with aGVHD (P < 0.01). Second, the expansion of CD8+ (P = 0.01) and CD8+ CD28- T cells (P = 0.03) was a characteristic finding in patients with aGVHD. Finally, we found that the percentages of Fas+CD8+, Fas+HLA-DR+ and FasL+ CD8+ cells were significantly increased. Fas antigen was highly coexpressed on most of the lymphocyte subsets, especially on CD8+ cells (P < 0.01), and also, significantly higher coexpression of FasL on CD8+ cells was found in patients with aGVHD (P < 0.01). In summary, an increase in the percentage of CD8+ cells which express Fas and its ligand in patients with aGVHD after BMT points to a possible role for the Fas/FasL pathway in the effector phase of aGVHD.

Eight-year experience of malignant lymphoma--survival and prognostic factors.

Several reports have suggested a geographic difference in the histopathologic characteristics and prognosis of malignant lymphoma around the world. We tried to evaluate the clinical and histopathologic characteristics, therapeutic outcomes, and prognostic features of malignant lymphoma, particularly in Korean patients. Three hundred and seventy-six adult patients with the initial histopathologic diagnosis of malignant lymphoma of Yonsei University College of Medicine over an 8-year period were analyzed, retrospectively, with the following results: 1) There were 47 cases of Hodgkin's disease (HD) (12.5%) and 329 of non-Hodgkin's lymphoma (NHL) (87.5%) with a 1:7 ratio. The most common histopathologic subtype of HD was mixed cellularity (44.7%), and that of NHL was intermediate grade (70.8%), especially diffuse large-cell type (44.1%), whereas follicular type was less common. In regard to the incidence of extranodal presentation, it is rare in HD (4.2%), but occurs in 49.8% of patients with NHL. 2) The complete remission (CR) rate was 91.5% in HD and 63.6% in NHL, and the 5-year and 7-year disease-free survival rates were 71.3% and 57.0% in HD; 67.0% and 49.6% in NHL. The 5-year and 8-year overall survival rates were 90.7% and 68.0% in HD; 65.2% and 60.2% in NHL. 3) By multivariate analysis, we found that age, performance status, histopathologic grade, stage, serum lactate dehydrogenase (LDH) and beta 2-microglobulin were the useful prognostic factors in predicting survival in NHL, while no definite prognostic factors were found in HD. Also, in NHL patients less than 60 years old, stage, serum LDH, and histopathologic grade were closely associated with their therapeutic outcomes. In conclusion, the characteristics of malignant lymphoma in our hospital differ from those in Western countries with respect to the clinical, histopathologic and immunophenotypic patterns, but the prognostic factors and overall therapeutic outcomes were quite comparable to those of other reports from Western countries.

Differential responses of CD34-positive acute myelogenous leukemic blasts to the costimulating effects of stem cell factor with GM-CSF and/or IL-3.

Stem cell factor (SCF), a c-kit ligand, has a preferential effect on the proliferation of several classes of immature hematopoietic progenitor cells in combination with GM-CSF or IL-3. To analyze the costimulatory role of SCF in leukemic growth, we investigated the effect of SCF in the presence of GM-CSF and/or IL-3 on isolated CD34-positive (CD34+) leukemic blasts from 15 patients with acute myelogenous leukemia (AML). Cultures of CD34+ cells from normal bone marrow were used as controls. When the proliferation of CD34+ AML blasts in the presence of GM-CSF and/or IL-3 were evaluated in vitro for the effects of SCF, two patterns emerged. In one pattern, CD34+ AML blasts responded with a significant increase in DNA synthesis and/or colony formation when SCF was used with GM-CSF and/or IL-3 relative to the growth with SCF alone; This result is consistent with those CD34+ bone marrow cells from normal donors. Six patients (40%) were included in this category. The addition of SCF as a single factor resulted in colony formation in all six of these cases. In the other pattern, nine of the patients (60%) had CD34+ leukemic cells whose growth with SCF plus either GM-CSF, IL-3, or GM-CSF+IL-3, was not significantly different from the growth noted in the presence of SCF alone. Among them seven cases that did not form colonies in response to SCF alone, and one case showing autocrine, background growth were included. In the six cases in which the costimulating effects of SCF were documented, CD34+ c-kit+ blasts comprised 50.5 +/- 18.7% of the CD34+ leukemic blasts-higher than 21.8 +/- 19.4% of cases in which the costimulating effect of SCF was not documented. In the cases showing high c-kit antigen expression (> or = 40%), SCF had a costimulatory effect in 71% (5/7) of the patients. In conclusion, our data indicate that CD34+ leukemic blasts from a good proportion of patients with AML did not respond to the costimulating effects of SCF in the presence of GM-CSF adn/or IL-3, in contrast to those CD34+ bone marrow cells from normal donors. The possible use of SCF for acute leukemia must await further cytogenetic and molecular studies, which should clarify the preferential costimulating role of SCF in normal hematopoiesis.

Monitoring of WT-1 gene expression in peripheral blood of patients with acute leukemia by semiquantitative RT-PCR; possible marker for detection of minimal residual leukemia.

The expression of the WT-1 gene which is found exclusively in human leukemic blasts frequently disappears from bone marrow of leukemia patients in complete remission (CR). Using semiquantitative RT-PCR, we investigated the expression of the WT-1 gene in peripheral bloods (PBs) of 33 patients with acute leukemia (AML 26; ALL 7) and monitored its expression after achievement of CR. None of the 6 normal controls expressed detectable levels of WT-1 transcripts (< 10(-4), background level), whereas 31 (93.9%) of 33 patients expressed variable levels of WT-1 transcripts (range, 10(-4) to 10(1)) at diagnosis. The level of WT-1 expression was not different between AML and ALL. By monitoring WT-1 gene expression in PB of 31 patients during CR, 5 patients relapsed (two from the 18 patients with undetectable levels of WT-1 gene expression and three from the 13 with WT-1 gene expression in low levels). Three of the 5 relapsed patients showed preceding reappearance or rise of WT-1 gene expression. From these results, we reconfirmed that the WT-1 gene is a pan-acute leukemic marker, which can be used to monitor minimal residual leukemia (MRL) after chemotherapy or in patients with CR.

Ex vivo generation of functional dendritic cells from mobilized CD34+ hematopoietic stem cells.

The ability to generate dendritic cells (DCs) in sizeable numbers has enormous implications for the development of clinically-effective antigen presentation procedures for cancer immunotherapy. We evaluated the generation of immunostimulatory DCs from peripheral blood CD34+ cells collected from healthy donors. CD34+ cells purified from leukapheresis product were seeded at 1 x 10(4) cells/mL in complete medium supplemented with GM-CSF, TNF alpha, IL-4, c-kit ligand, and flt3 ligand (FL). By day 14 of culture in the presence of GM-CSF + TNF alpha, the total cell number increased by 23.4 +/- 5.4-fold compared to the starting number of CD34+ cells. When the c-kit and FL were added to GM-CSF and TNF alpha, the cell number increased by 109.8 +/- 11.2-fold without affecting the immunophenotype of recovered cells. Flow cytometric analysis indicated that cells with the markers of mature dendritic cells, i.e., CD1a +CD14 -HLA-DR+, and CD80+CD86+HLA-DR+, constituted 49.0% +/- 7.5%, and 38.9% +/- 6.5%, respectively. This pattern of expression of surface antigen was unchanged whether the c-kit ligand and/or FL was added. The irradiated CD1a+HLA-DR+ cells recovered from in vitro cultures elicit a vigorous proliferation of allogeneic peripheral blood T-cells, irrespective of cytokine combinations. These findings provide advantageous tools for the large-scale generation of DCs that are potentially usable for clinical protocols of immunotherapy or vaccination in patients undergoing cancer treatment.