IgG4 related sclerosing encapsulating peritonitis with cocoon formation: An unusual and undescribed presentation.

IgG4-related sclerosing mesenteritis is a rare disease of mesentery of an unknown etiology which shows a constellation of histopathologic findings of lymphoplasmacytic inflammation with IgG4-positive plasma cells and marked fibrosis. This chronic inflammatory condition of mesentery forming an abdominal cocoon has never been described before to the best of our knowledge. Here, we report a patient with a history of subacute small bowel obstruction who was found to have an intra-abdominal encapsulating mass in the right iliac fossa and was finally diagnosed as IgG4-related sclerosing encapsulating peritonitis (abdominal cocoon) based on peroperative findings, histology and immunohistochemistry.

Fluorometric trace methanol detection in ethanol and isopropanol in a water medium for application in alcoholic beverages and hand sanitizers.

Detection of methanol (MeOH) in an ethanol (EtOH)/isopropanol ( i PrOH) medium containing water is crucial to recognize MeOH poisoning in alcoholic beverages and hand sanitizers. Although chemical sensing methods are very sensitive and easy to perform, the chemical similarities between the alcohols make MeOH detection very challenging particularly in the presence of water. Herein, the fluorometric detection of a trace amount of MeOH in EtOH/ i PrOH in the presence of water using alcohol coordinated Al(iii)-complexes of an aldehydic phenol ligand containing a dangling pyrazole unit is described. The presence of MeOH in the EtOH/ i PrOH causes a change of the complex geometry from tetrahedral (Td) to octahedral (Oh) due to the replacement of the coordinated EtOH/ i PrOH by MeOH molecules. The Td-complex exhibited fluorescence but the Oh-species did not, because of the intramolecular photo-induced electron transfer (PET). By interacting the Oh species with water, its one MeOH coordination is replaced by a water molecule followed by the proton transfer from the water to pyrazole-N which generates strong fluorescence by inhibiting the PET. In contrast, the water interaction dissociates the Td-complex to exhibit fluorescence quenching. The water induced reversal of the fluorescence response from the decrease to increase between the absence and presence of MeOH is utilized to detect MeOH in an EtOH/ i PrOH medium containing water with a sensitivity of ∼0.03-0.06% (v/v). The presence of water effected the MeOH detection and allows the estimation of the MeOH contamination in alcoholic beverages and hand sanitizers containing large amounts of water.

An aluminium fluorosensor for the early detection of micro-level alcoholate corrosion.

The detection of the dry alcoholate corrosion of aluminium is vital to design a corrosion resistive aluminium alloy for the storage and transportation of biofuel (methanol or ethanol). By synthesizing an Al3+ fluorescent probe operable in an alcoholic medium, we quantified the alcoholate corrosion in terms of the fluorometrically estimated soluble alkoxide (Al(OR)3) generation under nitrogen atmosphere. With time, a linear increase in corrosion with specific aluminium dissolution rate constants ∼2.0 and 0.9 µg per day per cm2 were estimated for aluminium and Al-7075 alloy, respectively. During open atmosphere monitoring, the adsorbed moisture converted small extent of Al(OR)3 to the insoluble Al(OH)3 at the alloy surface which retarded the alcoholate corrosion appreciably.

Protonation-induced pH increase at the triblock copolymer micelle interface for transient membrane permeability at neutral pH.

Achieving controlled membrane permeability using pH-responsive block copolymers is crucial for selective intercellular uptake. We have shown that the pH at the triblock-copolymer micelle interface as compared to its bulk pH can help regulate membrane permeability. The pH-dependent acid/base equilibriums of two different interface-interacting pH probes were determined in order to measure the interfacial pH for a pH-responsive triblock copolymer (TBP) micelle under a wide range of bulk pH (4.5-9.0). According to 1H NMR studies, both pH probes provided interfacial pH at a similar interfacial depth. We revealed that the protonation of the amine moiety at the micelle interface and the subsequent formation of a positive charge caused the interface to become relatively less acidic than that of the bulk as well as an increase in the bulk-to-interfacial pH deviation (ΔpH) from ∼0.9 to 1.9 with bulk pH reducing from 8.0 to 4.5. From the ΔpH vs. interface and bulk pH plots, the apparent and intrinsic protonations or positive charge formation pKa values for the micelle were estimated to be ∼7.3 and 6.0, respectively. When the TBP micelle interacted with an anionic large unilamellar vesicle (LUV) of a binary lipid (neutral and anionic) system at the bulk pH of 7.0, fluorescence leakage studies revealed that the pH increase at the micelle interface from that of the LUV interface (pH ∼ 5.5) made the micelle interface partially protonated/cationic, thereby exhibiting transient membrane permeability. Although the increasing interface protonation causes the interface to become relatively less acidic than the bulk at any bulk pH below 6.5, the pH increase at the micelle interface may not be sufficiently large to maintain the threshold for the amine-protonated condition for effecting transient leakage and therefore, a continuous leakage was observed due to the slow disruption of the lipid bilayer.

Porphyrin-Based Probe for Simultaneous Detection of Interface Acidity and Polarity during Lipid-Phase Transition of Vesicles.

Biochemical activities at a membrane interface are affected by local pH/polarity related to membrane lipid properties including lipid dynamics. pH and polarity at the interface are two highly interdependent parameters, depending on various locations from the water-exposed outer surface to the less polar inner surface. The optical response of common pH or polarity probes is affected by both the local pH and polarity; therefore, estimation of these values using two separate probes localized at different interface depths can be erroneous. To estimate interface pH and polarity at an identical interface depth, we synthesized a glucose-pendant porphyrin (GPP) molecule for simultaneous pH and polarity detection by a single optical probe. pH-induced protonation equilibrium and polarity-dependent π-π stacking aggregation for GPP are exploited to measure pH and polarity changes at the 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DMPG) membrane interface during DMPG phase transition. An NMR study confirmed that GPP is located at the interface Stern layer of DMPG large unilamellar vesicle (LUV). Using UV-vis absorption studies with an adapted analysis protocol, we estimated interface pH, or its deviation from the bulk phase value (ΔpH), and the interface polarity simultaneously using the same spectra for sodium dodecyl sulfate micelle and DMPG LUV. During temperature-dependent gel to liquid-crystalline phase transition of DMPG, there was ∼0.5 unit increase in ΔpH from approximately -0.6 to -1.1, with a small increase in the interface dielectric constant from ∼60 to 63. A series of spectroscopic data indicate the utility of GPP for evaluation of local pH/polarity change during lipid phase transition of vesicles.

A cross-sectional study on the role of stress in hyperglycemia and the effect of Mahatiktaka Kashaya (an Ayurvedic formulation) in its management.

BACKGROUND: Stress is a potential contributer to chronic hyperglycemia. Pitta Prakriti (body constitution) individuals are more prone to stress and the prevalence of type 2 diabetes in stressed out individuals is much more. Aim of study was to evaluate the role of stress in hyperglycemia in individuals of Pitta predominant constitution and to assess the effectiveness of Mahatiktaka Kashaya in stress-induced hyperglycemia. METHODOLOGY: A cross-sectional study was carried out in 100 Pitta predominant patients having fasting blood sugar level greater than 140 mg/dl, to find the association of stress and hyperglycemia, using International Stress Management Association questionnaire followed by open lebelled clinical trial with Mahatiktaka Kashaya (Decoction). Trial drug was administered at a dose of 15 ml twice daily for 14 days. Assessment was done before and after the treatment. OBSERVATION AND ANALYSIS: 80% of Pitta predominant individuals have reported stress-associated hyperglycemia. Overall effect of Mahatiktaka Kashaya in major domains of Stress Assessment Questionnaire, i.e., symptoms, stability and strategies was significant. Furthermore, the trial drug showed significant improvement in biochemical parameters of diabetes. CONCLUSION: The study concludes that there is significant association between stress and hyperglycemia in the individuals of Pitta constitution. Mahatiktaka Kashaya is found to be highly significant in stress-associated hyperglycemia in the above said group.

Born to Cry: A Genetic Dissection of Infant Vocalization.

Infant vocalizations are one of the most fundamental and innate forms of behavior throughout avian and mammalian orders. They have a critical role in motivating parental care and contribute significantly to fitness and reproductive success. Dysregulation of these vocalizations has been reported to predict risk of central nervous system pathologies such as hypoxia, meningitis, or autism spectrum disorder. Here, we have used the expanded BXD family of mice, and a diallel cross between DBA/2J and C57BL/6J parental strains, to begin the process of genetically dissecting the numerous facets of infant vocalizations. We calculate heritability, estimate the role of parent-of-origin effects, and identify novel quantitative trait loci (QTLs) that control ultrasonic vocalizations (USVs) on postnatal days 7, 8, and 9; a stage that closely matches human infants at birth. Heritability estimates for the number and frequency of calls are low, suggesting that these traits are under high selective pressure. In contrast, duration and amplitude of calls have higher heritabilities, indicating lower selection, or their importance for kin recognition. We find suggestive evidence that amplitude of infant calls is dependent on the maternal genotype, independent of shared genetic variants. Finally, we identify two loci on Chrs 2 and 14 influencing call frequency, and a third locus on Chr 8 influencing the amplitude of vocalizations. All three loci contain strong candidate genes that merit further analysis. Understanding the genetic control of infant vocalizations is not just important for understanding the evolution of parent-offspring interactions, but also in understanding the earliest innate behaviors, the development of parent-offspring relations, and the early identification of behavioral abnormalities.

Binding of phenazinium dye safranin T to polyriboadenylic acid: spectroscopic and thermodynamic study.

Here, we report results from experiments designed to explore the association of the phenazinium dye safranin T (ST, 3,7-diamino-2,8-dimethyl-5-phenylphenazinium chloride) with single and double stranded form of polyriboadenylic acid (hereafter poly-A) using several spectroscopic techniques. We demonstrate that the dye binds to single stranded polyriboadenylic acid (hereafter ss poly-A) with high affinity while it does not interact at all with the double stranded (ds) form of the polynucleotide. Fluorescence and absorption spectral studies reveal the molecular aspects of binding of ST to single stranded form of the polynucleotide. This observation is also supported by the circular dichroism study. Thermodynamic data obtained from temperature dependence of binding constant reveals that association is driven by negative enthalpy change and opposed by negative entropy change. Ferrocyanide quenching studies have shown intercalative binding of ST to ss poly-A. Experiments on viscosity measurements confirm the binding mode of the dye to be intercalative. The effect of [Na⁺] ion concentration on the binding process suggests the role of electrostatic forces in the complexation. Present studies reveal the utility of the dye in probing nucleic acid structure.

Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile X syndrome reveals limited, call type specific deficits.

Fragile X syndrome (FXS) is a well-recognized form of inherited mental retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1) gene. The gene is located on the long arm of the X chromosome and encodes fragile X mental retardation protein (FMRP). Absence of FMRP in fragile X patients as well as in Fmr1 knockout (KO) mice results, among other changes, in abnormal dendritic spine formation and altered synaptic plasticity in the neocortex and hippocampus. Clinical features of FXS include cognitive impairment, anxiety, abnormal social interaction, mental retardation, motor coordination and speech articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs) when isolated from their mothers. Whether those social ultrasonic vocalizations are deficient in mouse models of FXS is unknown. Here we compared isolation-induced USVs generated by pups of Fmr1-KO mice with those of their wild type (WT) littermates. Though the total number of calls was not significantly different between genotypes, a detailed analysis of 10 different categories of calls revealed that loss of Fmr1 expression in mice causes limited and call-type specific deficits in ultrasonic vocalization: the carrier frequency of flat calls was higher, the percentage of downward calls was lower and that the frequency range of complex calls was wider in Fmr1-KO mice compared to their WT littermates.

Dynamic correlation between whisking and breathing rhythms in mice.

Sniffing, a high-frequency, highly rhythmic inhalation and exhalation of air through the nose, plays an important role in rodent olfaction. Similarly, whisking, the active rhythmic movement of whiskers, plays an important role in rodent tactile sensation. Rodents whisk and sniff during exploratory behavior to sample odorants and surfaces. Whisking is thought to be coordinated with sniffing and normal respiratory behavior, but the precise temporal relationships between these movements are not known. Here, using direct measurements of whisking and respiratory movements, we examined the strength and temporal dynamics of the correlation between large-amplitude whisker movements and respiratory rhythm in mice. Whisking movements were detected using an optical sensor, and respiration was monitored with a thermistor placed close to the nostril. Our measurements revealed that breathing and whisking movements were significantly correlated only when the whisking rhythm was <5 Hz. Only a fraction (~13%) of all large-amplitude whisker movements occurred during episodes of high-frequency (>5 Hz) respiration typically associated with sniffing. Our results show that that the rhythms of respiratory and whisking movements are correlated only during low-frequency whisking and respiration. High-frequency whisking and sniffing behaviors are not correlated. We conclude that whisking and respiratory rhythms are generated by independent pattern-generating mechanisms.

Comprehensive motor testing in Fmr1-KO mice exposes temporal defects in oromotor coordination.

Fragile X syndrome (FXS; MIM #300624), a well-recognized form of inherited human mental retardation is caused, in most cases, by a CGG trinucleotide repeat expansion in the 5'-untranslated region of FMR1, resulting in reduced expression of the fragile X mental retardation protein (FMRP). Clinical features include macroorchidism, anxiety, mental retardation, motor coordination, and speech articulation deficits. The Fmr1 knockout (Fmr1-KO) mouse, a mouse model for FXS, has been shown to replicate the macroorchidism, cognitive deficits, and neuroanatomical abnormalities found in human FXS. Here we asked whether Fmr1-KO mice also display appendicular and oromotor deficits comparable to the ataxia and dysarthric speech seen in FXS patients. We employed standard motor tests for balance and appendicular motor coordination, and used a novel long-term fluid-licking assay to investigate oromotor function in Fmr1-KO mice and their wild-type (WT) littermates. Fmr1-KO mice performed equally well as their WT littermates on standard motor tests, with the exception of a raised-beam task. However, Fmr1-KO mice had a significantly slower licking rhythm than their WT littermates. Deficits in rhythmic fluid-licking in Fmr1-KO mice have been linked to cerebellar pathologies. It is believed that balance and motor coordination deficits in FXS patients are caused by cerebellar neurophathologies. The neuronal bases of speech articulation deficits in FXS patients are currently unknown. It is yet to be established whether similar neuronal circuits control rhythmic fluid-licking pattern in mice and speech articulation movement in humans.

High-precision, three-dimensional tracking of mouse whisker movements with optical motion capture technology.

The mystacial vibrissae or whiskers in rodents are sensitive tactile hairs emerging from both sides of the face. Rats and mice actively move these whiskers during exploration. The neuronal mechanisms controlling whisker movements and the sensory representation of whisker tactile information are widely studied as a model for sensorimotor processing in mammals. Studies of the natural whisker movement patterns during exploration and tactile examination are still in their early stages. Tracking the movements of whiskers is technically challenging as they move relatively fast and are very thin, particularly in mice. Existing systems detect light-beam interruptions by the whiskers or use high-speed video to track whisker movements in one or two-dimensions. Here we describe a method for tracking the movements of mouse whiskers in three-dimensions (3D) using optical motion capture technology (OMCT). OMCT tracks the movements of small retro-reflective markers attached to whiskers of a head-fixed mouse with a spatial resolution of <0.5 mm in all 3D and a temporal resolution of 5 ms (200 fps). The system stores the 3D coordinates of the marker's trajectories onto hard disk allowing a detailed analysis of movement trajectories bilateral coordination. The described method currently uses the minimum of two tracking cameras, which requires head-fixation for reliable tracking.

Design and synthesis of enediyne-based peptide with selective peptide-cleaving activity.

A hybrid peptide-enediyne molecule was synthesised and shown to undergo selective intramolecular peptide chain cleavage by the 1,4-diyl radical, the potential intermediate of the enediyne system.

A technique for stereotaxic recordings of neuronal activity in awake, head-restrained mice.

Neurophysiological recordings of brain activity during behavior in awake animals have traditionally been performed in primates because of their evolutionary close relationship to humans and comparable behavioral skills. However, with properly designed behavioral tasks, many fundamental questions about how the brain controls behavior can also be addressed in small rodents. Today, the rapid progress in mouse neurogenetics, including the development of mouse models of human brain disorders, provides unique and unparalleled opportunities for the investigation of normal and pathological brain function. The development of experimental procedures for the recording of neuronal activity in awake and behaving mice is an important and necessary step towards neurophysiological investigation of normal and pathological mouse brain function. Here we describe a method for stereotaxic recordings of neuronal activity from head-restrained mice during fluid licking. Fluid licking is a natural and spontaneous behavior in rodents, which mice readily perform under head-restrained conditions. Using a head-restrained preparation allows recordings of well-isolated single units at multiple sites during repeated experimental sessions. Thus, a large number of neurons can be tested for their relationship with behavior and detailed spatial maps of behavior related neuronal activity can be generated as exemplified here with recordings from lick-related Purkinje cells in the cerebellum.

Prenatal alcohol exposure delays acquisition and use of skilled reaching movements in juvenile rats.

Prenatal alcohol exposure (PAE) has been previously reported to result in behavioral and cognitive deficits that continue into adulthood. These deficits are often manifested by poor performance on higher-order cognitive motor tasks, difficulties in maintaining postural balance, slower reaction times, and deficits in fine motor performance. The central causes of these cognitive and motor deficits have been studied in human and animal models. Rats have been shown to be capable of performing skilled reaching and grasping movements with their forepaws that exhibit many components of skilled reaching also found in human and non-human primates. Whether PAE affects skilled reaching movements in rats is unknown. In the present study, we investigated the effect of PAE on skilled reaching and grasping behavior in rats. Pregnant Sprague-Dawley rats were intragastrically gavaged daily with alcohol at a dose of 6 g/kg body weight from gestation day one (G1) through G20 that yielded average blood alcohol levels between 265 and 343 mg/dL. Non-alcohol groups, pairfed (n=4) and chowfed (n=9), served as nutritionally-matched and normal controls, respectively to the alcohol treatment group (n=12). At 7 weeks of age, all rats were deprived of food for one day. The next day, rats were individually placed in test cages where food could only be accessed by reaching through a grid and grasping small food pellets (20 mg) on a tray. All rats were naive to the task. The major findings in this study are: a) PAE significantly increased the average number of minutes to make a successful skilled reach (Alc mean+/-SEM=97.3+/-16.9 min vs. non-Alc 52.3+/-9.6 min), b) once a successful skilled reach was learned, non-alcohol control rats were no better than Alc rats in using the skilled reach to acquire food, c) no significant differences between groups were observed in the amount of food consumption or changes in body weight during test sessions. These findings provide an important first step into the role that PAE plays for the learning of new skills and will lead to studies of central mechanisms underlying more complex skilled reaching behaviors.

Analysis of cerebellar function in Ube3a-deficient mice reveals novel genotype-specific behaviors.

Angelman syndrome (AS) is a childhood-onset neurogenetic disorder characterized by functionally severe developmental delay with mental retardation, deficits in expressive language, ataxia, appendicular action tremors and unique behaviors such as inappropriate laughter and stimulus-sensitive hyperexcitibility. Most cases of AS are caused by mutations which disrupt expression of maternal UBE3A. Although some progress has been made in understanding hippocampal-related memory and learning aspects of the disorder using Ube3a deficient mice, the numerous motoric abnormalities associated with AS (ataxia, action tremor, dysarthria, dysphagia, sialorrhea and excessive chewing/mouthing behaviors) have not been fully explored with mouse models. Here we use a novel quantifiable analysis of fluid consumption and licking behavior along with a battery of motor tests to examine cerebellar and other motor system defects in Ube3a deficient mice. Mice with a maternally inherited Ube3a deficiency (Ube3a(m-/p+)) show defects in fluid consumption behavior which are different from Ube3a(m-/p-) mice. The rhythm of fluid licking and number of licks per visit were significantly different among the three groups (m-/p-, m-/p+, m+/p+) and indicate that not only was fluid consumption dependent on Ube3a expression in the cerebellum, but may also depend on low levels of Ube3a expression in other brain regions. Additional neurological testing revealed defects in both Ube3a(m-/p+) and Ube3a(m-/p-) mice in rope climbing, grip strength, gait and a raised-beam task. Long-term observation of fluid consumption behavior is the first phenotype reported that differentiates between mice with a maternal loss of function versus complete loss of Ube3a in the brain. The neuronal and molecular mechanisms underlying mouse fluid consumption defects specifically associated with maternally inherited Ube3a deficiency may reveal important new insights into the pathobiology of AS in humans.