A 1.5-million-year record of orbital and millennial climate variability in the North Atlantic

Climate during the last glacial period was marked by abrupt instability on millennial timescales that included large swings of temperature in and around Greenland (Daansgard-Oeschger events) and smaller, more gradual changes in Antarctica (AIM events). Less is known about the existence and nature of similar variability during older glacial periods, especially during the early Pleistocene when glacial cycles were dominantly occurring at 41 kyr intervals compared to the much longer and deeper glaciations of the more recent period. Here, we report a continuous millennially resolved record of stable isotopes of planktic and benthic foraminifera at IODP Site U1385 (the "Shackleton Site") from the southwestern Iberian margin for the last 1.5 million years, which includes the Middle Pleistocene Transition (MPT). Our results demonstrate that millennial climate variability (MCV) was a persistent feature of glacial climate, both before and after the MPT. Prior to 1.2 Ma in the early Pleistocene, the amplitude of MCV was modulated by the 41 kyr obliquity cycle and increased when axial tilt dropped below 23.5° and benthic δ18O exceeded ∼3.8 ‰ (corrected to Uvigerina), indicating a threshold response to orbital forcing. Afterwards, MCV became focused mainly on the transitions into and out of glacial states (i.e. inceptions and terminations) and during times of intermediate ice volume. After 1.2 Ma, obliquity continued to play a role in modulating the amplitude of MCV, especially during times of glacial inceptions, which are always associated with declining obliquity. A non-linear role for obliquity is also indicated by the appearance of multiples (82, 123 kyr) and combination tones (28 kyr) of the 41 kyr cycle. Near the end of the MPT (∼0.65 Ma), obliquity modulation of MCV amplitude wanes as quasi-periodic 100 kyr and precession power increase, coinciding with the growth of oversized ice sheets on North America and the appearance of Heinrich layers in North Atlantic sediments. Whereas the planktic δ18O of Site U1385 shows a strong resemblance to Greenland temperature and atmospheric methane (i.e. Northern Hemisphere climate), millennial changes in benthic δ18O closely follow the temperature history of Antarctica for the past 800 kyr. The phasing of millennial planktic and benthic δ18O variation is similar to that observed for MIS 3 throughout much of the record, which has been suggested to mimic the signature of the bipolar seesaw - i.e. an interhemispheric asymmetry between the timing of cooling in Antarctica and warming in Greenland. The Iberian margin isotopic record suggests that bipolar asymmetry was a robust feature of interhemispheric glacial climate variations for at least the past 1.5 Ma despite changing glacial boundary conditions. A strong correlation exists between millennial increases in planktic δ18O (cooling) and decreases in benthic δ13C, indicating that millennial variations in North Atlantic surface temperature are mirrored by changes in deep-water circulation and remineralization of carbon in the abyssal ocean. We find strong evidence that climate variability on millennial and orbital scales is coupled across different timescales and interacts in both directions, which may be important for linking internal climate dynamics and external astronomical forcing. Copyright

Practice Nurses' views of their role in the management of Chronic Fatigue Syndrome/Myalagic Encephalitis: a qualitative study

<p>Abstract</p> <p>Background</p> <p>NICE guidelines suggest that patients with Chronic Fatigue Syndrome/Myalgic Encephalitis (CFS/ME) should be managed in Primary Care. Practice Nurses are increasingly being involved in the management of long-term conditions, so are likely to also have a growing role in managing CFS/ME. However their attitudes to, and experiences of patients with CFS/ME and its management must be explored to understand what barriers may exist in developing their role for this group of patients. The aim of this study was to explore Practice Nurses' understanding and beliefs about CFS/ME and its management.</p> <p>Methods</p> <p>Semi-structured interviews with 29 Practice Nurses. Interviews were transcribed verbatim and an iterative approach used to develop themes from the dataset.</p> <p>Results</p> <p>Practice nurses had limited understanding about CFS/ME which had been largely gained through contact with patients, friends, personal experiences and the media rather than formal training. They had difficulty seeing CFS/ME as a long term condition. They did identify a potential role they could have in management of CFS/ME but devalued their own skills in psychological intervention, and suggested counselling would be an appropriate therapeutic option. They recognised a need for further training and on going supervision from both medical and psychological colleagues. Some viewed the condition as contentious and held pejorative views about CFS/ME. Such scepticism and negative attitudes will be a significant barrier to the management of patients with CFS/ME in primary care.</p> <p>Conclusion</p> <p>The current role of Practice Nurses in the ongoing management of patients with CFS/ME is limited. Practice Nurses have little understanding of the evidence-base for treatment of CFS/ME, particularly psychological therapies, describing management options in terms of advice giving, self-help or counselling. Practice Nurses largely welcomed the potential development of their role in this area, but identified barriers and training needs which must be addressed to enable them to feel confident managing of patients with this condition. Training must begin by addressing negative attitudes to patients with CFS/ME.</p

Mediator Subunit 12 Is Required for Neutrophil Development in Zebrafish

Hematopoiesis requires the spatiotemporal organization of regulatory factors to successfully orchestrate diverse lineage specificity from stem and progenitor cells. Med12 is a regulatory component of the large Mediator complex that enables contact between the general RNA polymerase II transcriptional machinery and enhancer bound regulatory factors. We have identified a new zebrafish med12 allele, syr, with a single missense mutation causing a valine to aspartic acid change at position 1046. Syr shows defects in hematopoiesis, which predominantly affect the myeloid lineage. Syr has identified a hematopoietic cell-specific requirement for Med12, suggesting a new role for this transcriptional regulator

Insights into Protein Aggregation by NMR Characterization of Insoluble SH3 Mutants Solubilized in Salt-Free Water

Protein aggregation in vivo has been extensively associated with a large spectrum of human diseases. On the other hand, mechanistic insights into protein aggregation in vitro were incomplete due to the inability in solubilizing insoluble proteins for high-resolution biophysical investigations. However, a new avenue may be opened up by our recent discovery that previously-thought insoluble proteins can in fact be solubilized in salt-free water. Here we use this approach to study the NMR structural and dynamic properties of an insoluble SH3 mutant with a naturally-occurring insertion of Val22 at the tip of the diverging turn. The obtained results reveal: 1) regardless of whether the residue is Val, Ala, Asp or Arg, the insertion will render the first hNck2 SH3 domain to be insoluble in buffers. Nevertheless, all four mutants could be solubilized in salt-free water and appear to be largely unfolded as evident from their CD and NMR HSQC spectra. 2) Comparison of the chemical shift deviations reveals that while in V22-SH3 the second helical region is similarly populated as in the wild-type SH3 at pH 2.0, the first helical region is largely unformed. 3) In V22-SH3, many non-native medium-range NOEs manifest to define non-native helical conformations. In the meanwhile a small group of native-like long-range NOEs still persists, indicating the existence of a rudimentary native-like tertiary topology. 4) Although overall, V22-SH3 has significantly increased backbone motions on the ps-ns time scale, some regions still own restricted backbone motions as revealed by analyzing 15N relaxation data. Our study not only leads to the establishment of the first high-resolution structural and dynamic picture for an insoluble protein, but also shed more light on the molecular events for the nonhierarchical folding mechanism. Furthermore, a general mechanism is also proposed for in vivo protein aggregation triggered by the genetic mutation and posttranslational modification

A 1.5-million-year record of orbital and millennial climate variability in the North Atlantic

Abstract. Climate during the last glacial period was marked by abrupt instability on millennial timescales that included large swings of temperature in and around Greenland (Daansgard–Oeschger events) and smaller, more gradual changes in Antarctica (AIM events). Less is known about the existence and nature of similar variability during older glacial periods, especially during the early Pleistocene when glacial cycles were dominantly occurring at 41 kyr intervals compared to the much longer and deeper glaciations of the more recent period. Here, we report a continuous millennially resolved record of stable isotopes of planktic and benthic foraminifera at IODP Site U1385 (the “Shackleton Site”) from the southwestern Iberian margin for the last 1.5 million years, which includes the Middle Pleistocene Transition (MPT). Our results demonstrate that millennial climate variability (MCV) was a persistent feature of glacial climate, both before and after the MPT. Prior to 1.2 Ma in the early Pleistocene, the amplitude of MCV was modulated by the 41 kyr obliquity cycle and increased when axial tilt dropped below 23.5∘ and benthic δ18O exceeded ∼3.8 ‰ (corrected to Uvigerina), indicating a threshold response to orbital forcing. Afterwards, MCV became focused mainly on the transitions into and out of glacial states (i.e. inceptions and terminations) and during times of intermediate ice volume. After 1.2 Ma, obliquity continued to play a role in modulating the amplitude of MCV, especially during times of glacial inceptions, which are always associated with declining obliquity. A non-linear role for obliquity is also indicated by the appearance of multiples (82, 123 kyr) and combination tones (28 kyr) of the 41 kyr cycle. Near the end of the MPT (∼0.65 Ma), obliquity modulation of MCV amplitude wanes as quasi-periodic 100 kyr and precession power increase, coinciding with the growth of oversized ice sheets on North America and the appearance of Heinrich layers in North Atlantic sediments. Whereas the planktic δ18O of Site U1385 shows a strong resemblance to Greenland temperature and atmospheric methane (i.e. Northern Hemisphere climate), millennial changes in benthic δ18O closely follow the temperature history of Antarctica for the past 800 kyr. The phasing of millennial planktic and benthic δ18O variation is similar to that observed for MIS 3 throughout much of the record, which has been suggested to mimic the signature of the bipolar seesaw – i.e. an interhemispheric asymmetry between the timing of cooling in Antarctica and warming in Greenland. The Iberian margin isotopic record suggests that bipolar asymmetry was a robust feature of interhemispheric glacial climate variations for at least the past 1.5 Ma despite changing glacial boundary conditions. A strong correlation exists between millennial increases in planktic δ18O (cooling) and decreases in benthic δ13C, indicating that millennial variations in North Atlantic surface temperature are mirrored by changes in deep-water circulation and remineralization of carbon in the abyssal ocean. We find strong evidence that climate variability on millennial and orbital scales is coupled across different timescales and interacts in both directions, which may be important for linking internal climate dynamics and external astronomical forcing. NER

Integrating human health into the urban development and transport planning agenda : A summary and final conclusions

This book has brought together people from different sectors and disciplines including urban and transport planning, environment, public health and social sciences to document how urban and transport planning and related environmental exposures affect health and what could be the solutions to create healthier cities. Although the language and terminology used at times differ substantially, the main messages that come across are that improvements in urban and transport planning are essential and possible to improve public health

Actinidia DRM1 - An intrinsically disordered protein whose mRNA expression is inversely correlated with spring budbreak in kiwifruit

Intrinsically disordered proteins (IDPs) are a relatively recently defined class of proteins which, under native conditions, lack a unique tertiary structure whilst maintaining essential biological functions. Functional classification of IDPs have implicated such proteins as being involved in various physiological processes including transcription and translation regulation, signal transduction and protein modification. Actinidia DRM1 (Ade DORMANCY ASSOCIATED GENE 1), represents a robust dormancy marker whose mRNA transcript expression exhibits a strong inverse correlation with the onset of growth following periods of physiological dormancy. Bioinformatic analyses suggest that DRM1 is plant specific and highly conserved at both the nucleotide and protein levels. It is predicted to be an intrinsically disordered protein with two distinct highly conserved domains. Several Actinidia DRM1 homologues, which align into two distinct Actinidia-specific families, Type I and Type II, have been identified. No candidates for the Arabidopsis DRM1-Homologue (AtDRM2) an additional family member, has been identified in Actinidia