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Introduction: Many guidelines now recommend early rehabilitation for acute stroke patients. However, evidence remains lacking regarding the specific timings for initiation of various rehabilitation steps and management when complications are encountered in acute stroke rehabilitation. This survey aimed to investigate actual clinical situations in acute stroke rehabilitation in Japan and to improve the medical systems for rehabilitation and plan further studies. Methods: This nationwide, cross-sectional, web-based questionnaire survey was administered between February 7, 2022, and April 21, 2022, targeting all primary stroke centers (PSCs) in Japan. Among several components of the survey, this paper focused on the timing of the initiation of three rehabilitation steps (passive bed exercise; head elevation; and out-of-bed mobilization), along with the management of rehabilitation (continued or suspended) in the event of complications during acute stroke rehabilitation. We also investigated the influence of facility features on these contents. Results: Responses were obtained from 639 of the 959 PSCs surveyed (response rate: 66.6%). In cases of ischemic stroke and intracerebral hemorrhage, most PSCs initiated passive bed exercise on day 1, head elevation on day 1, and out-of-bed mobilization on day 2 (with day of admission defined as day 1). In cases with subarachnoid hemorrhage, rehabilitation steps were delayed compared to other stroke subtypes or showed wide variation depending on the facility. Passive bed exercise was accelerated by the presence of protocols for rehabilitation and weekend rehabilitation. Out-of-bed mobilization was accelerated by the presence of a stroke care unit. Facilities with board-certified rehabilitation doctors were cautious regarding the initiation of head elevation. Most PSCs suspended rehabilitation training in the event of symptomatic systemic/neurological complications. Conclusion: Our survey revealed the actual situation of acute stroke rehabilitation in Japan and indicated that some facility features appear to influence early increases in physical activity levels and early mobilization. Our survey provides fundamental data to improve the medical systems for acute stroke rehabilitation in the future. [ABSTRACT FROM AUTHOR]

A tetravalent GlcNAc pendant glycocluster was constructed with terminal biotin through C 6 linker. To acquire the multivalent carbohydrate-protein interactions, we synthesized a glycopolymer of tetrameric structure using N-acetyl- d -glucosamine (GlcNAc) as the target carbohydrate by the use of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as coupling reagent, followed by biotin-avidin complexation leading to the formation of glycocluster of avidin-biotin-GlcNAc conjugate (ABG complex). The dynamic light scattering (DLS) system was implied for size detection and to check the binding affinity of GlcNAc conjugate with a WGA lectin we use fluorometric assay by means of specific excitation of tryptophan at λ ex 295 nm and it was found to be very high K a ∼ 1.39 × 10 7 M −1 in case of ABG complex as compared to GlcNAc only K a ∼ 1.01 × 10 4 M −1 with the phenomenon proven to be due to glycocluster effect. [ABSTRACT FROM AUTHOR]

A polymerizable alcohol having 9 PEG repeats was prepared in order to mimic an oligosaccharide moiety. Sialyl α(2→3) lactose, which is known as a sugar moiety of GM3 ganglioside, was also prepared, and the polymerizable alcohol was condensed with the sialyl α(2→3) lactose derivative to afford the desired glycomonomer, which was further polymerized with or without acrylamide to give water-soluble glycopolymers. The glycopolymers had higher affinities than those of glycopolymers having sialyl lactose moieties with shorter aglycon moieties. [ABSTRACT FROM AUTHOR]

Highlights: [•] Saccharidic chiral dopants for nematic liquid crystals were synthesized from d-glucose. [•] The helical twisting power (HTP) values were evaluated. [•] The chiral dopants induced helices in the host nematic liquid crystals. [•] No relationship between HTP and specific rotation on the chiral dopants was observed in this study. [Copyright &y& Elsevier]

Purpose: To test whether diffusion tensor imaging could evaluate potential motor capability of patients with chronic cerebral infarction. Methods: We used constraint-induced movement therapy (CIMT) as a rehabilitation, which reveals potential motor capability. We also investigated the relationship between the outcome of CIMT and the ratio between fractional anisotropy values (rFA) in affected and unaffected sites of the corticospinal tract before CIMT. Imaging was performed in cerebral infarction patients (n = 14) and the rFA of the posterior limb of internal capsule (PLIC) was measured before CIMT. Patients were evaluated before and after CIMT using the Fugl-Meyer (F-M) assessment, Wolf Motor Function Test, Action Research Arm Test, and Motor Activity Log and association between PLIC- rFA and these scores was determined. Results: All patients showed an improvement in mobility following the 10-day CIMT session. Strong positive correlation was found only between F-M after CIMT and PLIC-rFA (r = 0.8098, p = 0.0004). A strong linear relationship was observed after CIMT. Conclusion: These data support PLIC-rFA as a new marker of the CIMT-induced improvement in motor function (F-M). [ABSTRACT FROM AUTHOR]

The article discusses a study that investigated the long-term effects after constraint-induced movement therapy with and without transfer package among post-stroke patients. The results of the study showed an increase in arm function after the intervention in both control and test groups, but six months later, only the transfer package group showed a consistent increase in arm function.

We assessed the relationship between fractional anisotropy (FA) values of magnetic resonance-diffusion tensor imaging (DTI) and long-term outcome (3-7 months after onset) in patients with hemiparesis after intracerebral hemorrhage (N = 12). DTI data were obtained on days 14-18. FA values within the cerebral peduncle were analyzed using a computer-automated method. Motor outcome of hemiparesis was evaluated using Brunnstrom stage (six-point scale: severe to normal) for separate shoulder/elbow/forearm, wrist/hand, and lower extremity functions when patients were discharged from a long-term rehabilitation facility 3-7 months after onset. In addition, the motor component of the functional independence measure (FIM-motor) was scored. The ratio of FA values in the affected hemisphere to those in the unaffected hemisphere (rFA) was assessed in relation to the clinical data (Spearman's rank correlation test, P < 0.05). Analysis revealed a statistically significant relationship between rFA and upper extremity function (R = 0.863 for shoulder/elbow/forearm; 0.834 for wrist/hand). Although statistically significant, the relationship between rFA and lower extremity function was less evident (R = 0.609). In contrast, analysis of rFA and FIM-motor scores did not reveal statistical significance. FA values within the cerebral peduncle are tightly associated with long-term outcomes of upper extremity function. [ABSTRACT FROM AUTHOR]

Abstract: Conversions of the C-5 acetamide group in sialic acid into two kinds of Cbond substituents were accomplished under Shotten–Baumann conditions. The polymerizable glycomonomers also contain a hydrophobic chain or hydroxyl group at the anomeric position. Radical polymerizations of the fully protected glycomonomers were carried out with acryl amide in the presence of ammonium persulfate (APS) and N,N,N′,N′-tetramethylethylenediamine (TEMED), followed by deprotection to furnish water-soluble glycopolymers. The activities of the deprotected glycopolymers and glycomonomers against human influenza viruses (H1N1 and H3N2) and avian influenza virus (H5N3) were evaluated. Biological evaluations showed that the glycomonomers containing a long hydrophobic chain at the anomeric position had both hemagglutination and neuraminidase inhibitory activities. [Copyright &y& Elsevier]

Abstract: A series of bi-fluorescence-labeled maltooligosaccharides that lead to fluorescence resonance energy transfer (FRET) was systematically synthesized. Effective FRETs were observed with all of the synthesized probes. Digestion of probes having tetra-, quintet-, hexa- or hepta-saccharidic chain lengths with human saliva α-amylase resulted in disappearance of FRET when an excitation wavelength of at 290nm was used followed by detection at ca. 520nm due to emission from the dansyl moiety. However, continuous FRET was observed when probes having di- or trisaccharidic chain lengths were used as substrates. In addition to the substrate characteristics based on saccharidic chain length, the reaction rates of digestion for the substrates by amylase were different and also depended on their saccharidic chain length. [Copyright &y& Elsevier]

Abstract: In order to develop novel influenza sialidase inhibitors, we constructed a library of glycoclusters composed of twelve types of sialylated dendrimers with thioglycosidic linkage that are resistant to hydrolysis by the sialidases. These sialodendrimers were synthesized by condensation reaction between a thiosialoside modified on the aglycon terminal end by a thioacetyl group and twelve types of carbosilane dendrimers having brominated terminal ends under deacetylation conditions, and temporal re-protection was performed for purification. Removal of all protection of the glycodendrimers was accomplished by transesterification and subsequent saponification to provide corresponding water-soluble glycodendrimers in good yields. For investigation of the structure–activity relationship, dendrimer scaffolds having differences in number of the sugar moieties, such as 3-, 4-, 6- and 12-functionalized dendrimers, and in linkage patterns, such as normal aliphatic linkage, ether- and amide-linkages. Biological evaluations of these glycodendrimers showed that all of the ether- and amide-elongated compounds had inhibitory potencies for the influenza sialidases in the mM range, while compounds having normal aliphatic linkage did not have any activities except for a 12-functionalized compound. [Copyright &y& Elsevier]

Preparation of photo-responsive carbosilane dendrimers bearing 4-phenylazobenzonitrile units on their molecular surface has been accomplished, and their both photo and thermal behaviors have also been characterized. These functional dendrimers suggest that the apparent molecular sizes of the cis-isomers are smaller than those of the corresponding trans-isomers, since the molecular diameter of these dendrimers would be shorter on the basis of trans→cis photo-isomerization of azobenzene. [ABSTRACT FROM AUTHOR]

The thioglycoside of Neu5Gc unit was synthesized from the Neu5Ac derivative in 4 steps. The thioglycoside of Neu5Gc as a glycosyl donor was allowed to react with various alcohols to afford the corresponding glycosides. [Display omitted] • A Neu5Gc unit was prepared from a Neu5Ac derivative. • Thioglycoside of Neu5Gc was synthesized as a glycosyl donor. • Glycosidation of the Neu5Gc derivative gave the desired Neu5Gc-related compound. • Reaction properties of the thioglycoside of Neu5Gc were investigated. Efficient synthesis of lauryl thioglycoside of Neu5Gc was accomplished from a known thioglycoside of Neu5Ac. The reactivities of the Neu5Gc thioglycoside for O -glycosidation by means of TMSOTf-NIS as a promoter system were investigated, and the thioglycoside showed good activities with simple alcohols. In addition to the simple alcohols, the reactivities of lauryl thioglycoside of Neu5Gc were also evaluated with glucose and lactose derivatives and the results suggested that the thioglycoside is a potential candidate for glycosidation as the glycosyl donor. [ABSTRACT FROM AUTHOR]

Objective: Examination of effectiveness of different sites of constraint-induced movement therapy (CI therapy) for upper-extremity impairment of patients after stroke. Subjects: Patients exhibiting moderate to slight upper-extremity impairment after stroke. Methods: The patients received a modified version of CI therapy for a cumulative total of 5 h daily for 10 days. Using Fugl-Meyer scores, shoulder/elbow/forearm, wrist and hand functions were separately assessed before and after treatment. To assess the site-specific effects of CI therapy, before and after scores were statistically compared at each site using Wilcoxon signed-rank tests. Relative effects were evaluated by paired comparison of the results at each site with, in turn, the results at every other site. Instances of single-score increments were, using standard chi-square tests, statistically isolated and compared. Results: Nineteen patients, 12–169 (median 31) months after stroke, were enrolled in this study and completed the protocol. Age range was 40–81 (median 65) years old and pretreatment Fugl-Meyer total scores spanned 31–64 (median 48). Analyses detected statistically significant improvements for wrist, hand and coordination but not for shoulder/elbow/forearm subcomponents. For the hand, at least single-point increments were observed in 74% of the population, while only 47% showed similar increments for the shoulder/elbow/forearm, and 53% for the wrist. Statistical analysis revealed that a higher proportion had increments in hand scores. Conclusions: Statistical analysis shows that CI therapy is most beneficial for treating hand function, suggesting an efficient application of this treatment. [ABSTRACT FROM AUTHOR]

Abstract: An efficient synthesis of a series of carbosilane dendrimers uniformly functionalized with α-thioglycoside of sialic acid was accomplished. The results of a preliminary study on biological responses against influenza virus sialidases using thiosialoside clusters showed that some of the glycodendrimers have inhibitory potencies against the sialidases. [Copyright &y& Elsevier]

Objective: To assess the relationships between independence levels of single motor-related Functional Independence Measure (FIM™) items and summed FIM-motor scores of patients with hemiplegia after stroke. Design: For each patient FIM scores were assessed 4 times during hospitalization. Ordinal logistic analyses were performed on group data. Subjects: Fifty patients with hemiplegia after stroke staying in a long-term rehabilitation facility. Results: Analyses revealed that FIM-motor scores accounted for much of the variability of independence levels for most of the single FIM™ items, including dressing upper body, and transfers to bed/chair/wheelchair and to toilet. For these items, the independence levels were proportionally associated with FIM-motor scores. For eating, higher FIM-motor scores (>60) were associated with modified independence and lower FIM-motor scores ( 60). Conclusion: For single FIM™ items, relative difficulty was comparable with results from previous literatures using Rasch analyses. Moreover, our results revealed that relative difficulty for single items varied greatly between independence levels. With regard to disability task targets, probability of independence evaluated from logistic modelling is an aid to efficient rehabilitation scheduling. [ABSTRACT FROM AUTHOR]

Objective: To examine the validity and applicability of logarithmic modelling for predicting functional recovery of stroke patients with hemiplegia. Design: Longitudinal postal survey. Subjects: Stroke patients with hemiplegia staying in a long-term rehabilitation facility, who had been referred from acute medical service 30–60 days after onset. Methods: Functional Independence Measure (FIM) scores were periodically assessed during hospitalization. For each individual, a logarithmic formula that was scaled by an interval increase in FIM scores during the initial 2–6 weeks was used for predicting functional recovery. Results: For the study, we recruited 18 patients who showed a wide variety of disability levels on admission (FIM scores 25–107). For each patient, the predicted FIM scores derived from the logarithmic formula matched the actual change in FIM scores. The changes predicted the recovery of motor rather than cognitive functions. Regression analysis showed a close fit between logarithmic modelling and actual FIM scores (across-subject R2 = 0.945). Conclusions: Provided with two initial time-point samplings, logarithmic modelling allows accurate prediction of functional recovery for individuals. Because the modelling is mathematically simple, it can be widely applied in daily clinical practice. [ABSTRACT FROM AUTHOR]

Our subjective sensory experiences are thought to be heavily shaped by interactions between expectations and incoming sensory information. However, the neural mechanisms supporting these interactions remain poorly understood. By using combined psychophysical and functional MRI techniques, brain activation related to the intensity of expected pain and experienced pain was characterized. As the magnitude of expected pain increased, activation increased in the thalamus, insula, prefrontal cortex, anterior cingulate cortex (ACC) and other brain regions. Pain-intensity-related brain activation was identified in a widely distributed set of brain regions but overlapped partially with expectation-related activation in regions, including the anterior insula and ACC. When expected pain was manipulated, expectations of decreased pain powerfully reduced both the subjective experience of pain and activation of pain-related brain regions, such as the primary so- matosensory cortex, insular cortex, and ACC. These results confirm that a mental representation of an impending sensory event can significantly shape neural processes that underlie the formulation of the actual sensory experience and provide insight as to how positive expectations diminish the severity of chronic disease states. [ABSTRACT FROM AUTHOR]

Pain is a temporally dynamic experience. Yet, in most instances, pain ratings are acquired in a static fashion and frequently require subjects to retrospectively evaluate the pain experience that occurred in a preceding interval of time. In order to determine which components of the real-time experience of pain contribute to static pain ratings, we obtained real-time (dynamic) and post-stimulus (static) ratings using a visual analogue scale during various of durations (5–30 s) of noxious thermal stimulation (43–49 °C). For both pain-intensity and pain-unpleasantness, real-time ratings revealed that pain adapted when stimulus temperatures were low to moderate and summated when stimulus temperature was high. Regression analyses examining both pain-intensity and pain-unpleasantness revealed that the mean response and the peak response of real-time ratings significantly contributed to post-stimulus ratings, while temporal components such as perceived duration of pain contributed minimally. Additional regression analyses revealed that mean and peak responses of real-time intensity ratings accounted for much of the variability of post-stimulus unpleasantness ratings whereas real-time unpleasantness ratings accounted for somewhat less of the variability of post-stimulus intensity ratings. Taken together, the close relationship between real-time and post-stimulus ratings of pain across stimulus conditions evoking both adaptation and temporal summation further confirms that post-stimulus, retrospective ratings of pain are valid measures of the real-time experience of pain. [Copyright &y& Elsevier]

One of the goals of human functional imaging studies is to interpret brain activation in the context of an individual’s subjective experience. However, functional magnetic resonance imaging (fMRI) studies usually employ a block design that consists of multiple epochs of stimulation; this strategy does not readily allow subjective responses to be assessed on a stimulus-by-stimulus basis. To address this issue, we developed a “single-epoch” design, consisting of a single stimulation period presented between two baseline periods. This allows subjective ratings to be acquired after each stimulus, while minimizing rating-induced confounds. To evaluate its sensitivity and utility, we obtained fMRI data using single-epoch and block designs (five stimuli between six baselines) and assessed regional brain activations evoked by both visual (a checkerboard pattern) and painful (noxious heat to right calf) stimuli. For both types of stimulation, data collected using the single-epoch design displayed activation patterns that were generally similar to those detected with the block design. Furthermore, only one single-epoch acquisition series was sufficient to detect bilateral activation in the visual cortex during visual stimulation and activation in the primary somatosensory cortex, the anterior cingulate cortex, and other regions during painful stimulation. In addition, analyses of a series of single-epoch data from a single individual revealed a stimulus-by-stimulus decrease in the activation in the anterior cingulate cortex that paralleled the decrease in the subject’s psychophysical responses. These findings confirm that the single-epoch design is sensitive to regional signal changes and serves as a viable alternative to the block design when the collection of subjective responses is of critical importance. [Copyright &y& Elsevier]

• Two polymers having α-mannoside moieties or dansyl fluorophores were conventionally prepared. • Efficient synthesis of glycopolymers having α-mannoside moieties and the fluorophores was accomplished. • Biological evaluations of glycopolymers—lectin interactions were performed. • Intermolecular FRET was clearly observed when fluorogenic glycopolymers were used. Quantitative evaluations of the binding affinities between glycopolymers and lectins in order to investigate the functionality of glycopolymers are of great importance. In this study, we developed fluorogenic glycopolymers that induce Förster resonance energy transfer (FRET) upon binding to lectins and we attempted directly to monitor the interaction followed by evaluation of the binding affinity on the basis of intermolecular FRET. Water-soluble glycopolymers with various polymer compositions containing mannose moieties as ligands for a lectin and dansyl moieties as fluorogenic chromophores for the FRET system were prepared, and the binding constant K a (M−1) with concanavalin A (Con A; mannose-binding lectin) was estimated on the basis of the change in fluorescence intensity caused by FRET. Fluorescence measurements revealed intermolecular FRET between the fluorogenic glycopolymer and Con A, and the binding constants were estimated to be 0.398×106 ∼ 2.40×106 (M−1). The results suggested that this method can be applied to evaluation of the interaction when the binding of a glycopolymer to a lectin results in little fluorescence change. [Display omitted] [ABSTRACT FROM AUTHOR]

This article describes Oreobolopsis and discusses the systematic position of it, with particular emphasis on the difference between the new genus and the related genera in the tribe Scirpeae of the Cyperaceae. The tribal characters of the new genus Oreobolopsis are rather clearly exhibited in the structures of its flowers and spikelets. The flowers of Oreobolopsis are all bisexual and possess six perianth segments, consisting of three each alternately disposed in two whorls. Three stamens are inserted alternately to the inner tepals, suggesting that the stamens in the inner whorl have disappeared.

Provides information on the taxonomic revision of Hypolytrum, based from the investigations of the genus in connection with the project Flora Neotropica. Number of species of the genus Hypolytrum; Source of the material for the revision; Botanical gardens and museums which are especially rich in Hypolytrum types.

Abstract: Synthesis of bi-fluorescence-labeled maltooligosaccharides for amylase assay was accomplished. Preliminary biological evaluation of both bi-fluorescence-labeled maltohexasaccharide and maltose using α-amylase was carried out, and the hexaosyl derivative showed unique variation on the basis of fluorescence resonance energy transfer (FRET). [Copyright &y& Elsevier]

[Display omitted] • Homopolymers and copolymers with histidine COOH, CONH 2 , and NH 2 were synthesized. • The polymers were incubated with bovine serum albumin and analyzed by SDS-PAGE. • Polymers with histidine COOH cleaved bovine serum albumin at pH 4.2 and pH 7.4. • Several polymers with specific histidine densities showed activity at pH 8.0. • Polymers with specific COOH density exhibited varying digestion patterns based on pH. Artificial enzymes with serine, aspartic acid, and histidine that mimic the catalytic triad of serine proteases have been studied. However, they were mainly investigated for their cleavage activity on low molecular-weight esters and amides, and there has been a lack of knowledge about their protein cleavage activity. We previously found that not only ternary polyacrylamides with serine, aspartic acid, and histidine but also homo-polyacrylamides with a single type of amino acid cleaved bovine and human serum albumins. These results suggested that the carboxy group, a common functional group in active polymers, may be involved in the expression of activity. In this study, we synthesized histidine polymers in which the carboxy group was changed to a carboxamido or amino group and investigated the relationships between structure and activity. Histidine homopolymers and histidine-acrylamide copolymers were incubated with bovine serum albumin at 37 °C for one week under different pH conditions and then analyzed by sodium dodecyl-sulfate polyacrylamide gel electrophoresis. In the case of histidine homopolymers, the carboxy-type homopolymers were active under weakly acidic to neutral conditions, while the carboxamido- and amino-type homopolymers were not active regardless of liquid properties. In the case of histidine-acrylamide copolymers, their activity was essentially the same as that of each type of histidine homopolymer, but for all types of copolymers, activity appeared under weakly basic conditions when the histidine monomer units were of a specific density. The carboxy-type copolymers with dual-mode activity showed different degradation patterns of bovine serum albumin under acidic and basic conditions. The structural features common to the active homopolymers and copolymers suggested that the carboxy group contributes to the activity under weakly acidic to neutral conditions, while the imidazole group of the histidine side chain and its density contribute to the activity under weakly basic conditions. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fischer's glycoside synthesis effectively worked with alcohols with longer aliphatic chains. • Glycopolymers having α-glycoside-type GlcNAc moieties were prepared. • Sugar densities on the glycopolymers were controlled. • Biological evaluations of glycopolymers—WGA were tested. • Glycopolymer having an appropriate sugar-density showed the highest affinity. Fischer's glycoside synthesis was applied to linker precursor alcohols of two different lengths having appropriate alkane chains to obtain the corresponding α-glycoside and it was found to be applicable with moderate yields. Water-soluble glycomonomers were systematically prepared from N -acetyl- d -glucosamine (GlcNAc) by introducing two kinds of alcohols having different methylene lengths. Typical radical polymerizations of the glycomonomers with acrylamide as a modulator for control of the distance between carbohydrate residues in water in the presence of ammonium persulfate (APS)- N , N , N' , N' -tetramethylethylenediamine (TEMED) gave a series of glycopolymers with various α-glycoside-type GlcNAc residue densities. Fluorometric analysis of the interaction of wheat germ agglutinin (WGA) with the glycopolymers was performed and the results showed unique binding specificities based on structural differences. [ABSTRACT FROM AUTHOR]

CM-Str (4-(Chloromethyl)styrene) was used as a useful starting material for the construction of a series of functional monomers. Substitution of the chlorine to the corresponding azide was performed, and the reduction of the azide proceeded smoothly to afford an aminostyrene, which was used as a common precursor for the preparation of functional monomers. Condensation of the amine with a fluorophore, biotin and carbohydrate was accomplished. Among the monomers, a carbohydrate monomer was polymerized with or without acrylamide as a model polymerization to yield the corresponding water-soluble glycopolymers, and biological evaluations of the glycopolymers for a lectin, and wheat germ agglutinin (WGA), were carried out on the basis of the fluorescence change of tryptophan in the WGA. [ABSTRACT FROM AUTHOR]

Bivalent glycoconjugates have a minimal valence with avidity potential on protein-carbohydrate interactions as well as simplicity of chemical structures enabling simple synthesis with low cost. Understanding the way to maximize the affinities of bivalent glycoconjugates is important for the development of cost-effective tools for therapeutic and diagnostic research. However, there has been little discussion about the effects of constraints imposed from ligand scaffolds on the binding abilities. We synthesized three kinds of biantennary N -acetylglucosamine glycosides with different scaffolds using isobutenyl bis(propargyl)ether as a common scaffold precursor. Decoration of the scaffold branches with GlcNAc moieties through copper-catalyzed azide-alkyne cycloaddition and grafting of the alkenyl focal point to another bivalent biotin dendron through thiol-ene and nucleophilic substitution reactions were successfully carried out in an orthogonal manner. The association constants of the ligands against wheat germ agglutinin were determined by a fluorometric titration assay. A bivalent biotin counterpart provided higher affinity than an isobutyl scaffold, whereas an isobutenyl scaffold yielded more enhancement than a bivalent biotin counterpart. The present work suggested that the constraint and steric bulk of ligand scaffolds are possible factors for improving binding properties of glycoconjugates against lectins or proteins. [ABSTRACT FROM AUTHOR]

Survivin, an inhibitor of the apoptosis protein family, is a potent tumor marker for diagnosis and prognosis. The enzyme-linked immunosorbent assay (ELISA) is one of the methods that has been used for detection of survivin. However, ELISA has several disadvantages caused by the use of conventional antibodies, and we have therefore been trying to develop a novel ELISA system using camelid single-domain antibodies (VHHs) as advantageous replacements. Here we report a supplemental approach to improve the VHH-polyclonal antibody sandwich ELISA for survivin detection. Iodoacetyl-functionalized pullulan was synthesized, and its thiol reactivity was characterized by a model reaction with l -cysteine. The thiophilic pullulan was applied to an immunoassay as an additive upon coating of standard assay plates with an anti-survivin VHH fusion protein with C -terminal cysteine. The results showed that the mole ratio of the additive to VHH had a significant effect on the consequent response. Mole ratios of 0.07, 0.7, and 7 led to 90% lower, 15% higher, and 69% lower responses, respectively, than the response of a positive control in which no additive was used. The background levels observed in any additive conditions were as low as that of a negative control lacking both VHH and the additive. These results indicate the applicability of the thiol-reactive pullulan as a response enhancer to VHH-based ELISA. [ABSTRACT FROM AUTHOR]

[Display omitted] Glycopolymers having sialyl α2-3 lactose moieties via longer spacer arms were systematically prepared from the corresponding glycomonomers. Radical polymerization of glycomonomers gave a series of glycopolymers displaying various sugar densities. Fluorometric analyses of wheat germ agglutinin (WGA) against the glycopolymers were conducted and the results showed unique binding specificities on the basis of sugar densities. [ABSTRACT FROM AUTHOR]

We assessed the relationship between fractional anisotropy (FA) values of magnetic resonance-diffusion tensor imaging (DTI) and long-term outcome in patients with hemiparesis after intracerebral hemorrhage (N =16). DTI data were obtained on days 14–18. FA values within the cerebral peduncle were analyzed using a computer-automated method. Motor outcome of hemiparesis was evaluated using Brunnstrom stage (six-point scale: severe to normal) for separate shoulder/elbow/forearm, wrist/hand, and lower extremity functions when patients were discharged from a long-term rehabilitation facility 2–7months after onset. In addition, the motor component of the functional independence measure (FIM-motor) was scored. The ratio of FA values in the affected hemisphere to those in the unaffected hemisphere (rFA) was assessed in relation to the clinical data (Spearman’s rank correlation test, P <0.05). Analysis revealed a statistically significant relationship between rFA and upper extremity function (R =0.841 for shoulder/elbow/forearm; 0.855 for wrist/hand). Although statistically significant, the relationship between rFA and lower extremity function (R =0.713) was less evident. The relationship between rFA and lower extremity and FIM-motor scores was moderate (R =0.579). These findings suggest that DTI is a potentially useful tool for outcome prediction, especially for upper extremity function. [Copyright &y& Elsevier]

[Display omitted] • A maleimide-terminated hexavalent carbosilane dendrimer was synthesized. • Thiol–maleimide reactions produced GlcNAc–dendrimer conjugates. • The glycodendrimers quenched the tryptophan fluorescence of WGA. • High binding affinities with nanomolar K D values were observed. We synthesized N -acetylglucosamine-terminated hexavalent carbosilane dendrimers and investigated their binding to wheat germ agglutinin (WGA). The glycodendrimers were prepared by the conjugation of 3-mercaptopropyl, 4-mercaptobutyl, or 5‑mercaptopentyl glycosides to maleimide-terminated hexavalent carbosilane dendrimers. Titration of WGA with the glycodendrimers yielded quenching of tryptophan fluorescence. All of the glycodendrimers exhibited high affinity with nanomolar dissociation constants (K D values). The best dendrimers were 1a and 1b with K D values of 6.5 ± 1.7 and 5.3 ± 1.7 nM, respectively. The magnitude of fluorescence quenching increased with decrease in the length of the thioalkyl spacer. Maleimide-pendant carbosilane dendrimers provide ready access to multivalent ligands with high-affinity potential. [ABSTRACT FROM AUTHOR]

[Display omitted] • Glycopolymer having GlcNAc moieties was prepared. • Sugar densities on the glycopolymers were controlled. • Degree of freedom of GlcNAc residue on the glycopolymers was controlled. • Biological evaluations of glycopolymers—lectin were performed. Four kinds of water-soluble carbohydrate monomers having different methylene numbers of polymerizable aglycons were systematically prepared from N -acetyl-D-glucosamine (GlcNAc). Typical radical polymerization in the presence of ammonium persulfate (APS)—tetramethylethylenediamine (TEMED) in water was applied for the monomers with acryl amide as a regulator for adjusting the average distance between carbohydrate residues, a series of glycopolymers having various densities of GlcNAc residues was obtained. Regulation of the polymers showed two pivotal points: one is the effect of lengths between carbohydrate residues and the polymer backbone and the other one is the influence of average densities of carbohydrates in the glycopolymer. Carbohydrate—protein interaction by means of the glycopolymer library for wheat germ agglutinin (WGA) as a model protein was investigated and the highest K a value was obtained when the glycopolymer having the longest methylene length and the ratio of 1:10 (sugar unit:acrylamide unit) was used as a substrate. [ABSTRACT FROM AUTHOR]

Highlights: [•] Chloromethylstyrene and N-acetyl-d-glucosamine (GlcNAc) were used for this study. [•] Simple modification of the starting materials gave the water-soluble glycomonomer. [•] A convenient access for glycopolymers was accomplished by radical polymerization. [•] The glycopolymers exhibited high affinity against WGA. [ABSTRACT FROM AUTHOR]

[Display omitted] • A hydrophobic Pba and a hydrophilic glycomonomer were polymerized. • The polymerization gave the corresponding water-soluble glycopolymer having Pba moieties. • Structural elucidation of the polymer was performed by 1H NMR. • The thermal property of the polymers was evaluated on the basis of TG-DTA measurement. • Uv–vis spectroscopic analysis of the polymer showed the characteristic absorption due to Pba. The first trial of incorporation of pheophorbide a (Pba) into a synthetic glycopolymer giving water-soluble ability was carried out, and the polymerization reaction of each monomer proceeded in DMSO to afford the desired glycopolymer having Pba side chains. Characterization of the polymer was performed by means of spectroscopic analyses and thermal studies, and the results supported the desired macromolecular architecture. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Methods: Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. Results: Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. Conclusions: The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain. [ABSTRACT FROM AUTHOR]

Abstract: An efficient synthesis of sialyllactosamine (SiaLacNAc) clusters using carbosilanes as core scaffolds has been accomplished by means of chemical and enzymatic approaches. N-Acetyl-d-glucosamine (GlcNAc) clusters having O-glycosidic linkage or S-glycosidic linkage were chemically synthesized from known intermediates in high yields. The GlcNAc clusters were first used as substrates for β1,4 galactosyl transferase using UDP-galactose (UDP-Gal) as a sugar source to provide corresponding N-acetyllactosamine clusters. Further sugar elongation of the LacNAc clusters was demonstrated using α2,3 sialyl transferase and CMP-neuraminic acid (CMP-NANA) to yield the corresponding SiaLacNAc clusters. [ABSTRACT FROM AUTHOR]

Abstract: Synthetic construction of fucosyl chitobiose [GlcNAcβ1→4(Fucα1→3)GlcNAc] as an allergy-associated carbohydrate epitope was accomplished from three building blocks. The trisaccharidic unit was further transformed into a carbohydrate monomer and polymerization of the glycomonomer proceeded smoothly to provide a series of glycopolymers having various carbohydrate densities. In addition to the organic syntheses, biological evaluations of the glycomonomer and the polymers were carried out and sugar-clustering effects were observed. [Copyright &y& Elsevier]

Abstract: Glycomonomers of sialic acid in which the acetamide group at C-5 was converted into two kinds of Cbond substituents were prepared and the fully protected glycomonomers were directly polymerized before deprotection steps. Radical polymerization with acrylamide in DMF in the presence of ammonium persulfate and N,N,N’,N’-tetramethylethylenediamine proceeded smoothly and gave corresponding sialopolymers. Interestingly glycomonomers had hemagglutination inhibitory activities not only for H1N1 but also for H3N2 of human influenza virus strains. [Copyright &y& Elsevier]

Abstract: A series of carbosilane dendrimers uniformly functionalized with sialyl lactose moieties (Neu5Acα2→3Galβ1→4Glc) was systematically synthesized, and biological evaluations for anti-influenza virus activity using the glycodendrimers were performed. The results suggested that the glycodendrimers had unique biological activities depending on the form of their core frame, and Dumbbell(1)6-amide type glycodendrimer 7 showed particularly strong inhibitory activities against human influenza viruses [A/PR/8/34 (H1N1) and A/Aichi/2/68 (H3N2)]. The results suggested that the structure–activity relationship (SAR) on the glycolibrary against various influenza viruses was observed, and dumbbell-shaped dendrimers as supporting carbohydrate moieties were found to be the most suitable core scaffolds in this study. [Copyright &y& Elsevier]

Abstract: An efficient separation between fully acetylated thiosialoside methyl esters and fully acetylated Neu5Ac2en methyl esters was accomplished by means of a size-exclusion chromatography (SEC) method. Purity determinations and structural elucidation of the isolated compounds were performed by a combination of elemental analyses and spectroscopic analyses, including IR, 1H, and 13C NMR, and mass spectroscopic analyses. [Copyright &y& Elsevier]

Abstract: An efficient synthesis of a series of carbosilane dendrimers uniformly functionalized with sialyl α(2→3) lactose (Neu5Acα(2→3)Galβ(1→4)Glcβ1→) moieties was accomplished. The results of a preliminary study on biological responses against influenza virus hemagglutinin, using the sialyl lactose clusters showed unique biological activities on the basis of the structure–activity relationship according to the carbosilane scaffolds. [Copyright &y& Elsevier]

Abstract: A conventional synthesis of α-thioglycoside of sialic acid as a glycomonomer was accomplished. Radical copolymerization of the glycomonomer with vinyl acetate proceeded smoothly to afford a new class of glycopolymers having thiosialoside residues, in which all protection was removed by a combination of transesterification and saponification to provide a water-soluble thiosialoside cluster. The results of a preliminary study on biological responses against influenza virus neuraminidases using the thiosialoside polymer as a candidate for a neuraminidase inhibitor showed that the glycopolymer has potent inhibitory activity against the neuraminidases. [Copyright &y& Elsevier]

Abstract: Carbosilane dendrimers periphery-functionalized with lactotriaose (GlcNAcβ1–3Galβ1–4Glc) with valencies of three, four, six, and twelve were prepared for use in a lectin-binding assay. A lactotriaose derivative was prepared from d-glucosamine and d-lactose derivatives. The N-Troc-protected glucosamine glycosyl donor and 3′-O-unprotected lactose glycosyl acceptor were condensed in the presence of silver trifluoromethanesulfonate and methylsulfenyl bromide to provide corresponding trisaccharide with new β-1-3 linkages in 92% yield. The protection group of the trisaccharide was transformed into an acetyl group. The 4-pentenyl glycoside was prepared from the acetate via glycosyl bromide. The alkene was converted into acetyl sulfide by addition of thioacetic acid under radical conditions. The lactotriaose unit was linked with carbosilane dendrimers to afford acetyl-protected glycodendrimers. De-O-acetylation of the dendrimers was carried out in the presence of sodium methoxide and then aq NaOH to give the desired lactotriaose clusters using a carbosilane dendrimer backbone. Their biological activities toward WGA were evaluated by fluorescence methods. The binding constants of free lactotriaose and trivalent, tetravalent, hexavalent, and dodecavalent glycodendrimers to WGA were determined to be 1.1×103, 4.4×104, 5.1×104, 2.8×106, and 1.3×106 M−1, respectively. The hexavalent glycodendrimer showed a 2500-fold larger binding effect than that of free lactotriaose. [Copyright &y& Elsevier]

Abstract: 4-Pentenyl (2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-(1→4)-(3,6-di-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1→3)-(2,6-di-O-benzoyl-β-d-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzoyl-β-d-glucopyranoside (4) was synthesized by regioselective glycosylation of 4-pentenyl (2,6,-di-O-benzoyl-β-d-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzoyl-β-d-glucopyranoside and (2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-(1→4)-3,6-di-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl chloride. By conversion of the protecting groups followed by thioacetylation, 4 was transformed into the corresponding lacto-N-neotetraose derivative, 5-(acetylthio)pentenyl (2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-(1→4)-O-(3,6-di-O-acetyl-2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→3)-(2,4,6-di-O-acetyl-β-d-galactopyranosyl)-(1→4)-2,3,6-tri-O-acetyl-β-d-glucopyranoside (6). The lacto-N-neotetraose derivative 6 was introduced into carbosilane dendrimer cores of three shapes, and three kinds of new carbosilane dendrimers peripherally functionalized by lacto-N-neotetraose were obtained. [Copyright &y& Elsevier]

Convenient access of a glycopolymer having N -acetyl- D -glucosamine (GlcNAc) residues was accomplished by means of radical polymerization of a simple GlcNAc monomer with or without acrylamide. Biological evaluations of glycopolymers displaying various carbohydrate contents were carried out by using fluorometric assays, and the results suggested that ratio of the sugar unit: acrylamide had a significant relation to affinities between carbohydrate—protein interactions. In this study, the unit ratio of 1:11.5 of carbohydrate: acrylamide was found to be the best ratio. Image 1 • A glycomonomer having GlcNAc was conventionally synthesized. • A series of glycopolymers having various densities of GlcNAc moieties was prepared. • Biological evaluations of glycopolymers—lectin were performed. • The contents of carbohydrate moieties—activity relationship of glycopolymers—lectin was investigated. [ABSTRACT FROM AUTHOR]

• Glycopolymer having GlcNAc moieties was conventionally prepared. • Efficient synthesis of glycopolymers having GlcNAc moieties and fluorophores was accomplished. • Biological evaluations of the glycopolymers—lectin were performed. • Intermolecular FRET was clearly observed using fluorogenic glycopolymers. A convenient assembly of fluorogenic glycopolymers having various polymer compositions was accomplished from the corresponding glycomonomer and dansyl monomer by means of radical polymerization, and the water-soluble glycopolymers gave typical fluorescence spectroscopic profiles due to the dansyl moieties on the glycopolymer in aqueous media. Biological evaluation of the polymer against wheat germ agglutinin (WGA) was accomplished on the basis of fluorescence changes due to tryptophan residues on WGA, and the affinities between the glycopolymers and WGA were estimated to be 4.7 × 105 to 9.3 × 105 M−1. In order to apply the fluorogenic glycopolymers for further biological measurements, efficient resonance energy transfer from tryptophan moieties on WGA to dansyl moieties on the fluorogenic glycopolymers was examined. FRET profiles of both fluorophores were similar compared to the binding profiles on the basis of fluorescence changes of tryptophan residues. This approach is applicable for the determination of an affinity constant between a carbohydrate and a lectin in which no fluorophore exists near the binding site. [ABSTRACT FROM AUTHOR]

• A prodrug-type neuraminidase substrate involving 4-nitroaniline was synthesized. • Neuraminidase activates the substrate to generate chromogenic 4-nitroaniline. • Neuraminidase is inactivated in the process of releasing 4-nitroaniline. Artificial substrates for probing neuraminidase activity are powerful tools for studying the physiological and pathological roles of neuraminidases. Most of the substrates are α- O -linked sialosides involving hydroxyl-containing reporters for visualization, and neuraminidase-catalyzed cleavage of the sialic acid residues directly activates the reporters. However, the use of amine-containing reporters has been avoided because α- N -linked sialosides are marginal substrates for neuraminidases. To expand the applicability of reporters to amine-containing compounds, we have focused on prodrug design. Herein we describe the synthesis and enzymatic study of a model substrate involving 4-nitroaniline as an amine-containing chromogenic reporter. The substrate can respond to neuraminidase from Clostridium perfringens. Neuraminidase-mediated hydrolysis of the sialic acid moiety of the substrate initiates self-immolative elimination of the linker moiety, leading the liberation of yellow-colored reporter 4-nitroaniline. The elimination process involves generation of quinone methide intermediate, which causes to neutralize neuraminidase. The substrate, thus, works as not only a chromogenic substrate but also a suicide inactivator. [ABSTRACT FROM AUTHOR]

[Display omitted] • Polyacrylamides functionalized with amino acids were synthesized. • Some polymers showed cleavage activity against bovine and human serum albumins. • The cleavage profiles of the active polymers differed from those of α-chymotrypsin. • At 50 °C, α-chymotrypsin lost activity, but the polymer showed better protein cleavage. Polyacrylamides with various compositions of serine, aspartic acid, and histidine, which are the amino acids involved in the catalytic triad of natural serine protease chymotrypsin, were synthesized and their protein cleavage activity was investigated. SDS-PAGE analysis showed that some of the synthesized ternary copolymers showed cleavage activity against bovine and human serum albumins. Polyacrylamides incorporating a single type of amino acid were also able to cleave the protein substrates. These homopolymers exhibited unique cleavage profiles and pH and temperature sensitivities that differed from those of α-chymotrypsin. The results indicate the potential of polymers functionalized with amino acids as proteolytic artificial enzymes. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Sugar-amino acid hybrid monomers were prepared. • Assembly of the monomers was accomplished by radical polymerization. • Affinities of the polymers against Stxs were examined. • High cluster-type polymers showed higher affinity than low cluster-type polymers. Abstract Synthetic assembly of sugar moieties and amino acids in order to create "sugar-amino acid hybrid polymers" was accomplished by means of simple radical polymerization of carbohydrate monomers having an amino acid-modified polymerizable aglycon. Amines derived from globotriaoside and lactoside as glycoepitopes were condensed with known carbobenzyloxy derivatives, including Z-Gly, Z- l -Ala and Z-β-Ala, which had appropriate spacer ability and a chiral center to afford fully protected sugar-amino acid hybrid compounds in good yields. After deprotection followed by acryloylation, the water-soluble glycomonomers were polymerized with or without acrylamide in the presence of a radical initiator in water to give corresponding copolymers and homopolymers, which were shown by SEC analysis to have high molecular weights. Evaluation of the biological activities of the glycopolymers against Shiga toxins (Stxs) was carried out, and the results suggested that glycopolymers having highly clustered globotriaosyl residues had high affinity against Stx2 (K D = 2.7∼4.0 µM) even though other glycopolymers did not show any affinity or showed very weak binding affinity. When Stx1 was used for the same assay, all of the glycopolymers having globotriaosyl residues showed high affinity (K D = 0.30∼1.74 µM). Interestingly, couple of glycopolymers having lactosyl moieties had weaker binding affinity against Stx1. In addition, when cytotoxicity assays were carried out for both Stxs, glycopolymers having highly clustered globotriaosyl residues showed higher affinity than that of the copolymers, and only highly clustered-type glycopolymers displayed neutralization potency against Stx2. [ABSTRACT FROM AUTHOR]

[Display omitted] • NMR analyses of CNN and its derivatives were performed. • Verification of standard acetylation for CNN was performed. • Complete protection of CNN was efficiently performed. Verification of acetylation by means of pyr—Ac 2 O for a cyclic α-nigerosyl-(1 → 6)-nigerose (CNN) was performed and the corresponding mono alcohol was obtained. Structural elucidation of CNN derivatives was carried out on the basis of NMR spectroscopic analyses. Complete protection by means of esterification and methylation was efficiently accomplished to yield fully protected compounds, and the results of NMR spectroscopic analyses of the products supported the perfect progress of the reaction. [ABSTRACT FROM AUTHOR]