Studies on the hill reaction activity of soluble chloroplast extracts final report

Hill reaction activity of soluble chloroplast extracts from spinac

Substrate specificity and the effect of calcium on Trypanosomabrucei metacaspase 2

Metacaspases are cysteine peptidases found only in yeast, plants and lower eukaryotes, including the protozoa. To investigate the extended substrate specificity and effects of Ca<sup>2+</sup> on the activation of these enzymes, detailed kinetic, biochemical and structural analyses were carried out on metacaspase 2 from Trypanosoma brucei (TbMCA2). These results reveal that TbMCA2 has an unambiguous preference for basic amino acids at the P<sub>1</sub> position of peptide substrates and that this is most probably a result of hydrogen bonding from the P<sub>1</sub> residue to Asp95 and Asp211 in TbMCA2. In addition, TbMCA2 also has a preference for charged residues at the P<sub>2</sub> and P<sub>3</sub>positions and for small residues at the prime side of a peptide substrate. Studies into the effects of Ca<sup>2+</sup> on the enzyme revealed the presence of two Ca<sup>2+</sup> binding sites and a reversible structural modification of the enzyme upon Ca<sup>2+</sup> binding. In addition, the concentration of Ca<sup>2+</sup> used for activation of TbMCA2 was found to produce a differential effect on the activity of TbMCA2, but only when a series of peptides that differed in P<sub>2</sub> were examined, suggesting that Ca<sup>2+</sup>activation of TbMCA2 has a structural effect on the enzyme in the vicinity of the S2 binding pocket. Collectively, these data give new insights into the substrate specificity and Ca<sup>2+</sup> activation of TbMCA2. This provides important functional details and leads to a better understanding of metacaspases, which are known to play an important role in trypanosomes and make attractive drug targets due to their absence in humans

Barriers to reporting non-motor symptoms to health-care providers in people with Parkinson's

Background: Non-motor symptoms (NMS) are common in Parkinson's disease (PD) and cause significant distress. A high rate of non-declaration of NMS by patients to healthcare providers (HCP) means that many NMS remain untreated. Current understanding of the factors preventing disclosure of NMS to HCPs is limited. The present study aimed to i) further assess the prevalence of NMS and associated distress, ii) establish current rates of NMS reporting across a range of sources, and iii) explore overall and any symptom specific barriers to help-seeking for NMS. Methods: 358 PD patients completed a cross-sectional survey of NMS severity, reporting and barriers to help-seeking. A series of Generalised Estimating Equations were used to determine whether barriers were symptom specific. Results: A mean of 10.5 NMS were reported by each patient. Rates of non-reporting of NMS ranged from 15 to 72% of those experiencing distressing symptoms. The most commonly reported barriers to help-seeking were acceptance of symptoms; lack of awareness that a symptom was associated with PD, and belief that no effective treatments were available. Symptom specific barriers were found for sexual dysfunction (embarrassment), unexplained pain and urinary problems (belief about lack of treatment availability). Conclusion: A diverse range of barriers prevent PD patients reporting NMS to HCPs and these barriers differ between NMS. The study provides the foundations for developing interventions to increase reporting by targeting individual NMS. Increasing rates of help-seeking for NMS by patients to their Parkinson's healthcare providers will increase appropriate clinical care which may improve quality of life and well-being

End of Life: A Family Narrative

This paper is based on ethnographic research that examines family reaction to an elderly husband and father's end of life. From a group of 30 families in our study (family defined as a widow aged 70 and over and two adult biological children between the ages of 40 and 60), we offer an extreme case example of family bereavement. We report our findings through the open-ended responses of a widow and two children who were interviewed ten months after the death of the husband and father. Three general themes emerged: (1) how the family imputes meaning to the end of life, (2) changes in the roles of family members, and (3) the family's ways of coping with the death, particularly through their belief system. A key finding is that the meaning family members find in their loved one's death is tied to the context of his death (how and where he died), their perception of his quality of life as a whole, and their philosophical, religious, and spiritual beliefs about life, death, and the afterlife that are already in place

Magnetic Reversal in Nanoscopic Ferromagnetic Rings

We present a theory of magnetization reversal due to thermal fluctuations in thin submicron-scale rings composed of soft magnetic materials. The magnetization in such geometries is more stable against reversal than that in thin needles and other geometries, where sharp ends or edges can initiate nucleation of a reversed state. The 2D ring geometry also allows us to evaluate the effects of nonlocal magnetostatic forces. We find a `phase transition', which should be experimentally observable, between an Arrhenius and a non-Arrhenius activation regime as magnetic field is varied in a ring of fixed size.Comment: RevTeX, 23 pages, 7 figures, to appear in Phys. Rev.

A single serine residue confers tetrodotoxin insensitivity on the rat sensory-neuron-specific sodium channel SNS

AbstractSensory neurons express a sodium channel (SNS) that is highly resistant to block by tetrodotoxin (IC50=60 μM). SNS is 65% homologous to the cardiac sodium channel, in which a single hydrophilic residue in the SS2 segment is critical for tetrodotoxin resistance. By site-directed mutagenesis, we have substituted phenylalanine for serine at the equivalent position in SNS: this mutated (S356F) SNS channel is functionally similar to wild-type SNS when expressed in Xenopus oocytes, but is potently blocked by tetrodotoxin and saxitoxin with IC50s of 2.8 nM and 8.2 nM, respectively. These data provide clues to the rational design of selective blockers of SNS with potential as analgesic drugs

School Entry Requirements and Coverage of Nontargeted Adolescent Vaccines

Low human papillomavirus (HPV) vaccination coverage is an urgent public health problem requiring action. To identify policy remedies to suboptimal HPV vaccination, we assessed the relationship between states’ school entry requirements and adolescent vaccination

Warm inflation model building

We review the main aspects of the warm inflation scenario, focusing on the inflationary dynamics and the predictions related to the primordial spectrum of perturbations, to be compared with the recent cosmological observations. We study in detail three different classes of inflationary models, chaotic, hybrid models and hilltop models, and discuss their embedding into supersymmetric models and the consequences for model building of the warm inflationary dynamics based on first principles calculations. Due to the extra friction term introduced in the inflaton background evolution generated by the dissipative dynamics, inflation can take place generically for smaller values of the field, and larger values of couplings and masses. When the dissipative dynamics dominates over the expansion, in the so-called strong dissipative regime, inflation proceeds with sub-planckian inflaton values. Models can be naturally embedded into a supergravity framework, with sugra corrections suppressed by the Planck mass now under control, for a larger class of K\"ahler potentials. In particular, this provides a simpler solution to the "eta" problem in supersymmetric hybrid inflation, without restricting the K\"ahler potentials compatible with inflation. For chaotic models dissipation leads to a smaller prediction for the tensor-to-scalar ratio and a less tilted spectrum when compared to the cold inflation scenario. We find in particular that a small component of dissipation renders the quartic model now consistent with the current CMB data.Comment: 22 pages, 5 figure

Facial expression of affect in children with Cornelia de Lange Syndrome

Background: Individuals with Cornelia de Lange syndrome (CdLS) have been reported to show comparatively high levels of flat and negative affect but there have been no empirical evaluations. In this study, we use an objective measure of facial expression to compare affect in CdLS with that seen in Cri du Chat syndrome (CDC) and a group of individuals with a mixed aetiology of intellectual disabilities (ID). Method: Observations of three groups of 14 children with CdLS, CDC and mixed aetiology of ID were undertaken when a one-to-one interaction was ongoing. Results: There was no significant difference between the groups in the duration of positive, negative or flat affect. However, the CdLS group displayed a significantly lower ratio of positive to negative affect than children in the other groups. Discussion: This difference partially confirms anecdotal observations and could be due to the expression of pain caused by health problems associated with CdLS or neurological expression of the CdLS gene in facial muscles related to expression of positive affect. However, further research is needed to directly test these possible associations. </p