Control of lipid organization and actin assembly during clathrin-mediated endocytosis by the cytoplasmic tail of the rhomboid protein Rbd2.

Clathrin-mediated endocytosis (CME) is facilitated by a precisely regulated burst of actin assembly. PtdIns(4,5)P2 is an important signaling lipid with conserved roles in CME and actin assembly regulation. Rhomboid family multipass transmembrane proteins regulate diverse cellular processes; however, rhomboid-mediated CME regulation has not been described. We report that yeast lacking the rhomboid protein Rbd2 exhibit accelerated endocytic-site dynamics and premature actin assembly during CME through a PtdIns(4,5)P2-dependent mechanism. Combined genetic and biochemical studies showed that the cytoplasmic tail of Rbd2 binds directly to PtdIns(4,5)P2 and is sufficient for Rbd2's role in actin regulation. Analysis of an Rbd2 mutant with diminished PtdIns(4,5)P2-binding capacity indicates that this interaction is necessary for the temporal regulation of actin assembly during CME. The cytoplasmic tail of Rbd2 appears to modulate PtdIns(4,5)P2 distribution on the cell cortex. The syndapin-like F-BAR protein Bzz1 functions in a pathway with Rbd2 to control the timing of type 1 myosin recruitment and actin polymerization onset during CME. This work reveals that the previously unstudied rhomboid protein Rbd2 functions in vivo at the nexus of three highly conserved processes: lipid regulation, endocytic regulation, and cytoskeletal function

Pelaksanaan Perpanjangan Uang Wajib Tahunan Otorita Sampai dengan Perpanjangan Hak Guna Bangunan di Kota Batam (Studi Kasus Kantor Notaris/PPAT Andreas Timothy, S.H., M.Kn.)

Problems often occur in the management of UWTO extension until the extension of the HGB is long term processing time. Whereas the request for an extension not new appliacation. The method used in this research is observation, interview, literature study, design and simulation. Research resut in the office of Notary/PPAT Andreas Timothy, S.H., M.Kn is form procedures for handling UWTO extension until extension of HGB, form completeness of the maintenance file extension UWTO, form completeness of maintenance file extension HGB and monitoring programs are designed with Microsoft Office Excel. The design of the completeness of this file is designed to enable employees of the Office Notary/PPAT to understand the procedures for handling UWTO extension until extension of HGB when explaining to clients. Key words: Extension, UWTO, HGB, Form, Design, Clients

Metagenomes in the Borderline Ecosystems of the Antarctic Cryptoendolithic Communities.

Antarctic cryptoendolithic communities are microbial ecosystems dwelling inside rocks of the Antarctic desert. We present the first 18 shotgun metagenomes from these communities to further characterize their composition, biodiversity, functionality, and adaptation. Future studies will integrate taxonomic and functional annotations to examine the pathways necessary for life to evolve in the extremes

Amygdala and Emotional Modulation of Multiple Memory Systems

Stress and anxiety can either enhance or impair memory, and the direction of the effect partially depends on the type of memory being affected. Behavioral or pharmacological stressors typically impair cognitive memory mediated by the hippocampus, but enhance stimulus-response habit memory mediated by the dorsolateral striatum. Evidence also indicates that the effect of emotion on different kinds of memory critically depends on a modulatory role of the basolateral amygdala (BLA). BLA modulation of multiple memory systems may be achieved through its glutamatergic projections to other brain regions, which may enhance stress hormone activity, modulate competition between memory systems, and alter synaptic plasticity. The neurobiology underlying the emotional modulation of multiple memory systems may be relevant to understand the impact of emotional arousal on the development and expression of human psychopathologies characterized by maladaptive habitual behaviors (e.g., drug addiction and relapse)

Shared Decision Making in the Psychiatric Inpatient Setting: An Ethnographic Study about Interprofessional Psychiatric Consultations

Shared decision making is increasingly receiving attention in health care and might improve both the quality of care and patient outcomes. Nevertheless, due to its complexity, implementation of shared decision making in clinical practice seems challenging. This ethnographic study aimed to gain a better understanding of how psychiatric inpatients and the interprofessional care team interact during regular interprofessional psychiatric consultations. Data were collected through participant observation on two different psychiatric wards in a large psychiatric hospital in Switzerland. The observation focused on the contextual aspects of interprofessional patient consultations, the communication and interaction as well as the extent to which patients were involved in decision making. Participants included patients, psychiatrists, junior physicians, nurses, psychologists, social workers and therapists. We observed 71 interprofessional psychiatric consultations and they differed substantially in both wards in terms of context (place and form) and culture (way of interacting). On the contrary, results showed that the level of patient involvement in decision making was comparable and depended on individual factors, such as the health care professionals' communication style as well as the patients' personal initiative to be engaged. The main topics discussed with the patients related to pharmacotherapy and patient reported symptoms. Health care professionals in both wards used a rather unidirectional communication style. Therefore, in order to promote patient involvement in the psychiatric inpatient setting, rather than to focus on contextual factors, consultations should follow a specific agenda and promoting a bidirectional communication style for all parties involved is strongly recommended

Association of ethanol with lipid membranes containing cholesterol, sphingomyelin and ganglioside: a titration calorimetry study

AbstractThe association of ethanol at physiologically relevant concentrations with lipid bilayers of different lipid composition has been investigated by use of isothermal titration calorimetry (ITC). The liposomes examined were composed of combinations of lipids commonly found in neural cell membranes: dimyristoyl phosphatidylcholine (DMPC), ganglioside (GM1), sphingomyelin and cholesterol. The calorimetric results show that the interaction of ethanol with fluid lipid bilayers is endothermic and strongly dependent on the lipid composition of the liposomes. The data have been used to estimate partitioning coefficients for ethanol into the fluid lipid bilayer phase and the results are discussed in terms of the thermodynamics of partitioning. The presence of 10 mol% sphingomyelin or ganglioside in DMPC liposomes enhances the partitioning coefficient by a factor of 3. Correspondingly, cholesterol (30 mol%) reduces the partitioning coefficient by a factor of 3. This connection between lipid composition and partitioning coefficient correlates with in vivo observations. Comparison of the data with the molecular structure of the lipid molecules suggests that ethanol partitioning is highly sensitive to changes in the lipid backbone (glycerol or ceramide) while it appears much less sensitive to the nature of the head group

Predicting frequency of suicide attempts of adolescent outpatients at Weskoppies Hospital using clinical and demographic characteristics

The prevention of suicide, particularly adolescent suicide, remains one of the biggest challenges in psychiatry. OBJECTIVES: To ascertain: (i) clinical and demographic characteristics; and (ii) possible associations between these characteristics and suicide attempt frequency in a selected patient group at Weskoppies Hospital over 4 months. METHODS: Fifty adolescent outpatients aged between 13 and 17 years with a history of one or more suicide attempts were interviewed to obtain demographic and clinical features. Chi-square and Fisher's exact tests assessed associations between these features and suicide attempt frequency. RESULTS: Of the subjects, 79% were aged between 15 and 17 years; they were predominantly female (62%) and Caucasian (83%). Mainstream and special education schools were equally represented. Three-quarters had reached grades 8 - 10, and 14% lived with both biological parents, 33% in places of safety and 37% with one divorced parent. The minority of caregivers had a history of alcohol abuse and other substance use. Twenty-nine per cent of the subjects had attempted suicide on more than 10 occasions and 23% had made a single attempt. The most common methods were wounding (74%), tablet overdose (34%) and hanging (20%). Psychiatric diagnoses included major depressive disorder (64%), bipolar disorder (38%), alcohol abuse (18%) and other substance abuse (24%). Familial features included depression, substance abuse, antisocial behaviour and suicide. Familial suicidal behaviour included suicide attempts by parents (85%), siblings (36%), aunts and uncles (31%) and cousins (44%). Physical and sexual abuse was reported in 52% of families. CONCLUSION: Many findings and profiles of other studies were confirmed and point to school and home environments, family psychopathology and psychiatric diagnoses as factors associated with adolescent suicide attempts. Associations between the frequency of suicide attempts and the demographic and clinical characteristics were statistically inconclusive.http://www.sajp.org.za/index.php/saj

The First Structure of an RNA m5C Methyltransferase, Fmu, Provides Insight into Catalytic Mechanism and Specific Binding of RNA Substrate

AbstractThe crystal structure of E. coli Fmu, determined at 1.65 Å resolution for the apoenzyme and 2.1 Å resolution in complex with AdoMet, is the first representative of the 5-methylcytosine RNA methyltransferase family that includes the human nucleolar proliferation-associated protein p120. Fmu contains three subdomains which share structural homology to DNA m5C methyltransferases and two RNA binding protein families. In the binary complex, the AdoMet cofactor is positioned within the active site near a novel arrangement of two conserved cysteines that function in cytosine methylation. The site is surrounded by a positively charged cleft large enough to bind its unique target stem loop within 16S rRNA. Docking of this stem loop RNA into the structure followed by molecular mechanics shows that the Fmu structure is consistent with binding to the folded RNA substrate