Microplastics in environment: global concern, challenges, and controlling measures.

Plastic pollution in various forms has emerged as the most severe environmental threat. Small plastic chunks, such as microplastics and nanoplastics derived from primary and secondary sources, are a major concern worldwide due to their adverse effects on the environment and public health. Several years have been spent developing robust spectroscopic techniques that should be considered top-notch; however, researchers are still trying to find efficient and straightforward methods for the analysis of microplastics but have yet to develop a viable solution. Because of the small size of these degraded plastics, they have been found in various species, from human brains to blood and digestive systems. Several pollution-controlling methods have been tested in recent years, and these methods are prominent and need to be developed. Bacterial degradation, sunlight-driven photocatalyst, fuels, and biodegradable plastics could be game-changers in future research on plastic pollution control. However, recent fledgling steps in controlling methods appear insufficient due to widespread contamination. As a result, proper regulation of environmental microplastics is a significant challenge, and the most equitable way to manage plastic pollution. Therefore, this paper discusses the current state of microplastics, some novel and well-known identification techniques, strategies for overcoming microplastic effects, and needed solutions to mitigate this planetary pollution. This review article, we believe, will fill a void in the field of plastic identification and pollution mitigation research.

Effectiveness of daily rinsing of alfalfa sprouts with aqueous chlorine dioxide and ozonated water on the growth of Listeria monocytogenes during sprouting.

Alfalfa sprouts have been implicated in multiple foodborne disease outbreaks. This study evaluated the growth of Listeria monocytogenes during sprouting of alfalfa seeds and the effectiveness of daily chlorine dioxide & ozone rinsing in controlling the growth. Alfalfa seeds inoculated with L. monocytogenes were sprouted for 5 days (25°C) with a daily aqueous ClO2 (3 ppm, 10 min) or ozone water (2 ppm, 5 min) rinse. Neither treatment significantly reduced the growth of L. monocytogenes on sprouting alfalfa seeds. The initial level of L. monocytogenes was 3·44 ± 0·27, which increased to c. 7·0 log CFU per g following 3 days of sprouting. There was no significant difference in the bacterial population between the treatment schemes. Bacterial distribution in roots (7·63 ± 0·511 log CFU per g), stems (7·51 ± 0·511 log CFU per g) and leaves (7·41 ± 0·511 log CFU per g) were similar after 5 days. Spent sanitizers had significantly lower levels of bacterial populations compared to the spent distilled water control. The results indicated that sprouting process provides a favourable condition for the growth of L. monocytogenes and the sanitizer treatment alone may not be able to reduce food safety risks. SIGNIFICANCE AND IMPACT OF THE STUDY: Sprouts are high-risk foods. Consumption of raw sprouts is frequently associated with foodborne disease outbreaks. Optimum sprouting procedure involves soaking seeds in water followed by daily water rinsing to maintain a moist environment that is also favourable for the growth of pathogenic micro-organisms. The present study emphasized the potential food safety risks during sprouting and the effect of applying daily sanitizer rinsing in the place of water rinsing to reduce those risks. The finding of this study may be useful in the development of pre-harvest and post-harvest risk management strategies.

Oleanolic acid from antifilarial triterpene saponins of Dipterocarpus zeylanicus induces oxidative stress and apoptosis in filarial parasite Setaria digitata in vitro.

Absence of a drug that kills adult filarial parasites remains the major challenge in eliminating human lymphatic filariasis (LF); the second leading cause of long-term and permanent disability. Thus, the discovery of novel antifilarial natural products with potent adulticidal activity is an urgent need. In the present study, methanol extracts of leaves, bark and winged seeds of Dipterocarpus zeylanicus (Dipterocarpaceae) were investigated for macro and microfilaricidal activity. Two antifilarial triterpene saponins were isolated from winged seed extracts by bioactivity guided chromatographic separation and identified using Nuclear Magnetic Resonance and mass spectroscopic analysis as oleanolic acid 3-O-ß-D- glucopyranoside (1) (IC50 = 20.54 µM for adult worms, 19.71 µM for microfilariae ) and oleanolic acid 3-O-α-L-arabinopyranoside (2) (IC50 = 29.02 µM for adult worms, 25.99 µM for microfilariae). Acid hydrolysis of both compounds yielded oleanolic acid (3) which was non or least toxic to human peripheral blood mono nuclear cells (Selectivity index = >10) while retaining similar macrofilaricidal (IC50 = 38.4 µM) and microfilaricidal (IC50 = 35.6 µM) activities. In adult female worms treated with 50 and 100 µM doses of oleanolic acid, condensation of nuclear DNA, apoptotic body formation and tissue damage was observed by using Hoechst 33342 staining, TUNEL assay and Hematoxylin and Eosin staining respectively. A dose dependent increase in caspase 3/CED3 activity and decrease in total protein content were also observed in these parasites. A dose dependant DNA fragmentation was observed in adult parasites and microfilariae. Decreased levels of reduced glutathione (GSH) and elevated levels of glutathione S transferase (GST), superoxide dismutase (SOD) and reactive oxygen species (ROS) were also observed in parasites treated with oleanolic acid indicating an oxidative stress mediated apoptotic event. Compound 3/oleanolic acid was thus identified as a potent and safe antifilarial compound in vitro.

Airborne fungal cell fragments in homes in relation to total fungal biomass.

Fungal exposure may induce respiratory symptoms. The causative agents are compounds in the fungal cell wall. Fragments of microbes may be present in air samples but are not measurable using conventional spore counting or by the determination of viable organisms. This study assesses the proportion of fungal cell biomass and endotoxin in different particle size fractions in air samples from homes. Air samples were collected from 15 homes using a cyclone sampler, collecting particles in three aerodynamic size fractions: <1.0, 1.0-1.8, and >1.8 µm. N-Acetylhexosaminidase (NAHA) was determined as a marker of fungal cell biomass. Endotoxin was determined using the Limulus amebocyte lysate method. NAHA and endotoxin in the size range <1.0 µm comprised up to 63% (mean 22.7%) and 96.3% (mean 22.6%) of the total concentrations, respectively. There were significant relationships between the amounts of NAHA and endotoxin in the total amount and in the size fraction >1.8 µm but not in the smaller fractions. The results demonstrate significant amounts of fungal cell biomass and endotoxin in particles <1.0 µm. Homes with reported mold damage had a lower concentration of NAHA in particles <1.0 µm than homes without mold damage. To assess airborne exposure for diagnostic and preventive purposes, measurement techniques that include this fraction should be considered.

Stenotrophomonas, Mycobacterium, and Streptomyces in home dust and air: associations with moldiness and other home/family characteristics.

Respiratory illnesses have been linked to children's exposures to water-damaged homes. Therefore, understanding the microbiome in water-damaged homes is critical to preventing these illnesses. Few studies have quantified bacterial contamination, especially specific species, in water-damaged homes. We collected air and dust samples in twenty-one low-mold homes and twenty-one high-mold homes. The concentrations of three bacteria/genera, Stenotrophomonas maltophilia, Streptomyces sp., and Mycobacterium sp., were measured in air and dust samples using quantitative PCR (QPCR). The concentrations of the bacteria measured in the air samples were not associated with any specific home characteristic based on multiple regression models. However, higher concentrations of S. maltophilia in the dust samples were associated with water damage, that is, with higher floor surface moisture and higher concentrations of moisture-related mold species. The concentrations of Streptomyces and Mycobacterium sp. had similar patterns and may be partially determined by human and animal occupants and outdoor sources of these bacteria.

A rare case of Goldenhar syndrome with radial aplasia.

Goldenhar syndrome (GS) is a well-recognised condition characterised by variable degree of uni- or bilateral involvement of craniofacial structures involving first and second branchial arches manifesting ocular and auricular anomalies and also vertebral defect. This syndrome presents at birth and its exact aetiology is still unknown. The affections of the neural crest cells may have some role in the multiple malformations of the GS. We present a teenaged female case who attended the Orthopaedic Outpatient Department to receive handicapped certificate in Bankura Sammilani Medical College and Hospital. She had multiple skeletal abnormalities, which included hemifacial microsomia, vertebral malformations in the form of scoliosis, distorted pelvis, but the most striking feature was the absence of thumb and aplasia of radius of left side. She did not suffer from any ocular or auricular abnormalities, neither from any cardiological, urogenital or gastroenteric ones. Radial defects associated with GS might represent a subset within this spectrum. Our case probably belongs to this subset, therefore is a very rare one.

Participatory asset mapping and photovoice interviews to scope cultural and community resources to reduce alcohol harm in Chitwan, Nepal.

AIMS: To scope the breadth of existing cultural and community assets and how alcohol drinkers and community health workers perceived them in relation to reducing alcohol-related harm. METHODS: The study was conducted in Chitwan, south-central Nepal, which has considerable alcohol problems. Participatory asset mapping was conducted using field notes, photography, and through engaging with communities to explore how community assets affect alcohol consumption. Semi-structured photovoice interviews were conducted with harmful/hazardous drinkers (AUDIT score 8 to 19) and community health workers. Purposive and snowball sampling were used to recruit participants. During interviews, participants used their photographs to reflect on how community assets influenced alcohol use. Thematic framework analysis was used to analyse the data. RESULTS: We recruited 12 harmful/hazardous drinkers (3 females) and 6 health workers (2 females). The mean AUDIT score of the former was 12.17 (SD ±2.86). Thematic analysis of the photovoice interviews produced three themes: 'influences and impact of families and communities'; 'culture and spirituality'; and 'nature and the environment'. The community mapping produced five assets that promoted alcohol consumption: (1) availability; (2) advertising; (3) negative attitudes towards users; (4) festivals/gatherings; and (5) illiteracy/poverty. Six assets that discouraged consumption were: (1) legislation restricting use; (2) community organisations; (3) cultural/spiritual sites; (4) healthcare facilities; (5) family and communities; and (6) women's community groups. Those from certain ethnic groups consumed more alcohol, experienced more family discord, or felt stigmatised due to their drinking. Assets 'festivals/gatherings' and 'negative attitudes toward users' and the theme 'family and communities' concerned with relationships and community activities were perceived to both promote and reduce alcohol use. CONCLUSIONS: This study provides new insight into a variety of cultural and community assets that promote and reduce alcohol use. The study identifies new possibilities to build on visual participatory and arts-based methods that have potential to be effectively implemented at scale.

Inadequacy of the risk factor based approach to detect gestational diabetes mellitus.

OBJECTIVE: To evaluate the present risk factor based approach in diagnosis of gestational diabetes mellitus (GDM) in Sri Lanka in comparison with new guidelines proposed by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). METHODS: A community based cross sectional descriptive study was conducted among pregnant women with gestational age of 24-28 weeks and residing in Anuradhapura district. All eligible pregnant women from selected Medical Officers of Health areas were invited to participate. The 75 g oral glucose tolerance test was carried out among all participants. RESULTS: According to IADPSG criteria, 36 (8.9%) of pregnant women had GDM, compared to 29 (7.2%) according to WHO criteria. Prevalence of GDM in the study population (positive by one or both methods) was 10.6% (n=43) (95% CI 7.9-13.9%). Of these 43 women,22 (51.1%) had positive results by both methods. Seven (16.3%) and 14 (32.6%) mothers were positive only according to WHO and IADPSG criteria respectively. Out of 29 mothers who fulfilled WHO criteria, only one had an abnormal fasting plasma glucose, but 28 had abnormal 2 hour values. A total of 170 (42.0%) participants had at least one risk factor or early indicator of GDM. A risk based approach would have detected only 22 GDM patients according to IADPSG criteria, missing 14 cases (38.9%) who did not have any of the risk factors for GDM. CONCLUSIONS: The risk factor based approach misses more than one third of GDM cases. Urgent revision of current GDM screening guidelines is recommended.

Decreased mortality in coronavirus disease 2019 associated mucormycosis with aspirin use: a retrospective cohort study.

OBJECTIVE: Rhino-orbito-cerebral mucormycosis is a rapidly progressive disease with high mortality rates of about 60 per cent. The increasing incidence of rhino-orbito-cerebral mucormycosis in coronavirus disease 2019 patients in India and worldwide has become a matter of concern owing to the case fatality rate. This study explored the use of low dose aspirin in decreasing the mortality rate of coronavirus disease 2019 associated mucormycosis. METHOD: This was a retrospective observational study. Patients suffering from post-coronavirus disease 2019 mucormycosis were included in the study. Each patient was treated with surgical debridement and systemic amphotericin B. Low dose aspirin was added, and mortality rates were compared with the patients who did not receive aspirin. RESULTS: The demographic data and rhino-orbito-cerebral mucormycosis staging between the two groups were not significantly different. There was a statistically significant difference in mortality outcomes between the two groups (p = 0.029) and a 1.77 times higher risk of dying for patients not receiving aspirin. Kaplan-Meier survival indicated that patients receiving aspirin had better survival rates (p = 0.04). CONCLUSION: Low dose aspirin improves survival rates in coronavirus disease 2019 associated mucormycosis.

Influence of spontaneous calcium events on cell-cycle progression in embryonal carcinoma and adult stem cells.

Spontaneous Ca(2+) events have been observed in diverse stem cell lines, including carcinoma and mesenchymal stem cells. Interestingly, during cell cycle progression, cells exhibit Ca(2+) transients during the G(1) to S transition, suggesting that these oscillations may play a role in cell cycle progression. We aimed to study the influence of promoting and blocking calcium oscillations in cell proliferation and cell cycle progression, both in neural progenitor and undifferentiated cells. We also identified which calcium stores are required for maintaining these oscillations. Both in neural progenitor and undifferentiated cells calcium oscillations were restricted to the G1/S transition, suggesting a role for these events in progression of the cell cycle. Maintenance of the oscillations required calcium influx only through inositol 1,4,5-triphosphate receptors (IP(3)Rs) and L-type channels in undifferentiated cells, while neural progenitor cells also utilized ryanodine-sensitive stores. Interestingly, promoting calcium oscillations through IP(3)R agonists increased both proliferation and levels of cell cycle regulators such as cyclins A and E. Conversely, blocking calcium events with IP(3)R antagonists had the opposite effect in both undifferentiated and neural progenitor cells. This suggests that calcium events created by IP(3)Rs may be involved in cell cycle progression and proliferation, possibly due to regulation of cyclin levels, both in undifferentiated cells and in neural progenitor cells.

3α-Dimethyl-amino-20-(N-methyl-acetamido)-pregn-5-ene.

The title compond, C(26)H(44)N(2)O, is an steroidal alkaloid isolated from the medicinally important plant Sarcococca saligna. The mol-ecule consists of four fused rings (A-D), having chair, half-chair, chair and envelope conformations, respectively. The dimethyl-amino group is axially oriented on ring A, whereas the (N-methyl-acetamido)-ethyl group is attached equatorially on ring D. The crystal structure is stabilized only by van der Waals forces.

Surface acoustic wave assisted depinning of magnetic domain walls.

We investigate the effects of high frequency strain on the depinning of magnetic domain walls in perpendicular anisotropy materials. Micron wide stripes of [Co(0.3 nm)/Pt(0.6 nm)]5are patterned between a pair of identical inter-digital transducers that generate high frequency (114.8 MHz) standing surface acoustic waves. We use magneto-optical Kerr effect microscopy to characterize the thermally-assisted depinning of domain walls at defect sites within the strips. Our results show that the excitation of the domain walls with surface acoustic waves results in an increase in their depinning probabilities by approximately a factor of 10. Our data are consistent with a model in which the magnetoelastic anisotropies induced by the acoustic waves modulate the energy barriers that pin the domain walls. These results suggest an alternative route to domain wall depinning in thin films and nanostructures and are relevant to the development of racetrack memories, where domain wall pinning can result in reduced velocities and non-deterministic motion.

The Band-Gap Studies of Short-Period CdO/MgO Superlattices.

Trends in the behavior of band gaps in short-period superlattices (SLs) composed of CdO and MgO layers were analyzed experimentally and theoretically for several thicknesses of CdO sublayers. The optical properties of the SLs were investigated by means of transmittance measurements at room temperature in the wavelength range 200-700 nm. The direct band gap of {CdO/MgO} SLs were tuned from 2.6 to 6 eV by varying the thickness of CdO from 1 to 12 monolayers while maintaining the same MgO layer thickness of 4 monolayers. Obtained values of direct and indirect band gaps are higher than those theoretically calculated by an ab initio method, but follow the same trend. X-ray measurements confirmed the presence of a rock salt structure in the SLs. Two oriented structures (111 and 100) grown on c- and r-oriented sapphire substrates were obtained. The measured lattice parameters increase with CdO layer thickness, and the experimental data are in agreement with the calculated results. This new kind of SL structure may be suitable for use in visible, UV and deep UV optoelectronics, especially because the energy gap can be precisely controlled over a wide range by modulating the sublayer thickness in the superlattices.

Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development.

BACKGROUND: One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification and the genes that regulate chromatin. AT-rich interactive domain 1B (ARID1B), a chromatin modifier, has been linked to autism spectrum disorder and to affect rare and inherited genetic variation in a broad set of NDDs. METHODS: A novel preclinical mouse model of Arid1b deficiency was created and validated to characterize and define neuroanatomical, behavioral and transcriptional phenotypes. Neuroanatomy was assessed ex vivo in adult animals and in vivo longitudinally from birth to adulthood. Behavioral testing was also performed throughout development and tested all aspects of motor, learning, sociability, repetitive behaviors, seizure susceptibility, and general milestones delays. RESULTS: We validated decreased Arid1b mRNA and protein in Arid1b+/- mice, with signatures of increased axonal and synaptic gene expression, decreased transcriptional regulator and RNA processing expression in adult Arid1b+/- cerebellum. During neonatal development, Arid1b+/- mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b+/- mice showed low motor skills in open field exploration and normal three-chambered approach. Arid1b+/- mice had learning and memory deficits in novel object recognition but not in visual discrimination and reversal touchscreen tasks. Social interactions in the male-female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviors were observed. Brains of adult Arid1b+/- mice had a smaller cerebellum and a larger hippocampus and corpus callosum. The corpus callosum increase seen here contrasts previous reports which highlight losses in corpus callosum volume in mice and humans. LIMITATIONS: The behavior and neuroimaging analyses were done on separate cohorts of mice, which did not allow a direct correlation between the imaging and behavioral findings, and the transcriptomic analysis was exploratory, with no validation of altered expression beyond Arid1b. CONCLUSIONS: This study represents a full validation and investigation of a novel model of Arid1b+/- haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs.

Effect of Yarcha Gumba (O sinensis) on Male Reproductive System in Rat.

The present study was undertaken to assess the aphrodisiac effect of O sinensis. It was a pre-clinical experimental case-control study performed in the Department of Pharmacology, RG Kar Medical College, Kolkata, India; from February 2019 to March 2019 using Wister rat model. One group of rats was given the test drug suspension (10mg/kg body weight) and the control group animals received the same volume of vehicle devoid of drug orally for 10 days. Sexual behaviour of individual rats was studied on 9th day of treatment with oestrogenized female Wister rats. On 10th day of treatment the animals were sacrificed by decapitation. After collection of blood sera from each animal; serum LH, FSH, testosterone and nitric oxide were assessed. Histological assessment of testes was done. Improved sexual behaviour, hypertrophy of Leydig cells, significant increase in serum LH (1.248 vs. 1.448mIU/ml), FSH (0.324 vs. 0.413mIU/ml) testosterone (3.120 vs. 4.498ng/ml) and nitric oxide (0.01757 vs. 0.02690nM/ml) were noted. Elevated NO titre in animals treated with O sinensis extract might be the cause of good erection capacity and increased libido in them. Nevertheless, result of the present study points that the active principle of O sinensis also acts on LHRH receptors present in pituitary gonadotrophs evidenced by significant increase in serum LH and FSH and indicating great aphrodisiac property.

Antibacterial activities of the extracts, fractions and isolated compounds from Canarium patentinervium Miq. against bacterial clinical isolates.

BACKGROUND: Canarium patentinervium leaves are used by the local indigenous people of Malaysia for wound healing. The current study is undertaken to screen the comprehensive antibacterial activity of the leaves and barks extracts, fractions and isolated compounds from this plant. Bioassay guided fractionation was also undertaken to deeply evaluate the antibacterial activity of the water fraction of the leaves extract. This is to provide preliminary scientific evidence to the ethnopharmacology usage of this plant by investigating antibacterial properties of the plant and its isolated constituents. METHODS: Bio-assay guided fractionation and subsequent isolation of compounds using open column chromatography. The antibacterial activity against gram positive and gram negative ATCC strain and resistant clinical strains were evaluated using microtiter broth dilution method to determine minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill assay. The chemical structure of the isolated compounds from the water fraction of the ethanol extract of leaves was elucidated using Nuclear Magnetic Resonance (NMR). RESULTS: The ethanol extract of the leaves and barks showed antimicrobial activity against all four ATCC and eight clinical isolates. The ethanol extract of the leaves and the corresponding water fraction had good activity against MRSA S. aureus. (MIC: 250 µg/ml) and had bactericidal effect on eight of the clinical strains (MSSA,MRSA, oxacillin-resistant CONS, oxacillin-sensitive CONS, Enterococcus faecalis, Klebsiela species, Kleb pneumoniae ESBL and Candida parapsilosis). Further phytochemical investigation of the water fraction of the crude ethanol extract of leaves afforded compound 7 (hyperin) and compound 8 (cynaroside) that had bactericidal activity against tested bacterial species (MIC 50 µg/ml and 100 µg/ml). The two compounds were isolated from this genus for the first time. CONCLUSIONS: These results may provide a rational support for the traditional use of Canarium patentinervium Miq. in infections and wound healing, since the antimicrobial compounds isolated were also present in the leaves extract.

Plant growth-promoting endophytic bacteria augment growth and salinity tolerance in rice plants.

Salt stress negatively affects growth and development of plants. However, it is hypothesized that plant growth-promoting endophytic bacteria can greatly alleviate the adverse effects of salinity and can promote growth and development of plants. In the present research, we aimed to isolate endophytic bacteria from halotolerant plants and evaluate their capacity for promoting crop plant growth. The bacterial endophytes were isolated from selected plants inhabiting sand dunes at Pohang beach, screened for plant growth-promoting traits and applied to rice seedlings under salt stress (NaCl; 150 mm). Out of 59 endophytic bacterial isolates, only six isolates, i.e. Curtobacterium oceanosedimentum SAK1, Curtobacterium luteum SAK2, Enterobacter ludwigii SAK5, Bacillus cereus SA1, Micrococcus yunnanensis SA2, Enterobacter tabaci SA3, resulted in a significant increase in the growth of Waito-C rice. The cultural filtrates of bacterial endophytes were tested for phytohormones, including indole-3-acetic acid, gibberellins and organic acids. Inoculation of the selected strains considerably reduced the amount of endogenous ABA in rice plants under NaCl stress, however, they increased GSH and sugar content. Similarly, these strains augmented the expression of flavin monooxygenase (OsYUCCA1) and auxin efflux carrier (OsPIN1) genes under salt stress. In conclusion, the pragmatic application of the above selected bacterial strains alleviated the adverse effects of NaCl stress and enhanced rice growth attributes by producing various phytohormones.

Translational outcomes in a full gene deletion of ubiquitin protein ligase E3A rat model of Angelman syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by developmental delay, impaired communication, motor deficits and ataxia, intellectual disabilities, microcephaly, and seizures. The genetic cause of AS is the loss of expression of UBE3A (ubiquitin protein ligase E6-AP) in the brain, typically due to a deletion of the maternal 15q11-q13 region. Previous studies have been performed using a mouse model with a deletion of a single exon of Ube3a. Since three splice variants of Ube3a exist, this has led to a lack of consistent reports and the theory that perhaps not all mouse studies were assessing the effects of an absence of all functional UBE3A. Herein, we report the generation and functional characterization of a novel model of Angelman syndrome by deleting the entire Ube3a gene in the rat. We validated that this resulted in the first comprehensive gene deletion rodent model. Ultrasonic vocalizations from newborn Ube3am-/p+ were reduced in the maternal inherited deletion group with no observable change in the Ube3am+/p- paternal transmission cohort. We also discovered Ube3am-/p+ exhibited delayed reflex development, motor deficits in rearing and fine motor skills, aberrant social communication, and impaired touchscreen learning and memory in young adults. These behavioral deficits were large in effect size and easily apparent in the larger rodent species. Low social communication was detected using a playback task that is unique to rats. Structural imaging illustrated decreased brain volume in Ube3am-/p+ and a variety of intriguing neuroanatomical phenotypes while Ube3am+/p- did not exhibit altered neuroanatomy. Our report identifies, for the first time, unique AS relevant functional phenotypes and anatomical markers as preclinical outcomes to test various strategies for gene and molecular therapies in AS.

Ubiquitin-mediated activation of TAK1 and IKK.

Transforming growth factor beta activated kinase-1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, has emerged as a key regulator of signal transduction cascades leading to the activation of the transcription factors nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1). Stimulation of cells with cytokines and microbial pathogens results in the activation of TAK1, which subsequently activates the I-kappa B kinase complex (IKK) and mitogen-activated protein (MAP) kinases, culminating in the activation of NF-kappaB and AP-1, respectively. Recent studies have shown that polyubiquitination of signalling proteins through lysine (Lys)-63-linked polyubiquitin chains plays an important role in the activation of TAK1 and IKK. Unlike Lys-48-linked polyubiquitination, which normally targets proteins for degradation by the proteasome, Lys-63-linked polyubiquitin chains act as scaffolds to assemble protein kinase complexes and mediate their activation through proteasome-independent mechanisms. The concept of ubiquitin-mediated activation of protein kinases is supported by the discoveries of ubiquitination and deubiquitination enzymes as well as ubiquitin-binding proteins that function upstream of TAK1 and IKK. Recent biochemical and genetic studies provide further insights into the mechanism and function of ubiquitin signalling and these advances will be the focus of this review.