Near-infrared Observations of Be/X-ray Binary Pulsar A0535+262

We present results obtained from an extensive near-infrared spectroscopic and photometric observations of the Be/X-ray binary A0535+262/HDE 245770 at different phases of its ~111 day orbital period. This observation campaign is a part of the monitoring programme of selective Be/X-ray binary systems aimed at understanding the X-ray and near-IR properties at different orbital phases, especially during the periastron passage of the neutron star. The near-IR observations were carried out using the 1.2 m telescope at Mt. Abu IR observatory. Though the source was relatively faint for spectroscopic observations with 1.2 m telescope, we monitored the source during the 2011 February--March giant outburst to primarily investigate whether any drastic changes in the near-IR JHK spectra take place at the periastron passage. Changes of such a striking nature were expected to be detectable in our spectra. Photometric observations of the Be star show a gradual and systematic fading in the JHK light curves since the onset of the X-ray outburst that could suggest a mild evacuation/truncation of the circumstellar disc of the Be companion. Near-IR spectroscopy of the object shows that the JHK spectra are dominated by the emission lines of hydrogen Brackett and Paschen series and HeI lines at 1.0830, 1.7002 and 2.0585 micron. The presence of all hydrogen emission lines in the JHK spectra, along with the absence of any significant change in the continuum of the Be companion during X-ray quiescent and X-ray outburst phases suggest that the near-IR line emitting regions of the disc are not significantly affected during the X-ray outburst.Comment: 10 Pages, 5 Figures, Accepted for publication in Res. in Astronomy and Astrophysic

Infrared studies of the Be star X Per

Photometric and spectroscopic results are presented for the Be star X Per/HD 24534 from near-infrared monitoring in 2010-2011. The star is one of a sample of selected Be/X-ray binaries being monitored by us in the near-IR to study correlations between their X ray and near-IR behaviour. Comparison of the star's present near-IR magnitudes with earlier records shows the star to be currently in a prominently bright state with mean J, H, K magnitudes of 5.49, 5.33 and 5.06 respectively. The JHK spectra are dominated by emission lines of HeI and Paschen and Brackett lines of HI. Lines of OI 1.1287 and 1.3165 micron are also present and their relative strength indicates, since OI 1.1287 is stronger among the two lines, that Lyman beta fluorescence plays an important role in their excitation. Recombination analysis of the HI lines is done which shows that the Paschen and Brackett line strengths deviate considerably from case B predictions. These deviations are attributed to the lines being optically thick and this supposition is verified by calculating the line center optical depths predicted by recombination theory. Similar calculations indicate that the Pfund and Humphrey series lines should also be expected to be optically thick which is found to be consistent with observations reported in other studies. The spectral energy distribution of the star is constructed and shown to have an infrared excess. Based on the magnitude of the IR excess, which is modeled using a free-free contribution from the disc, the electron density in the disc is estimated and shown to be within the range of values expected in Be star discs.Comment: Accepted for publication in MNRAS, 7 pages, 6 figure

Characterization of the Raf Kinase Inhibitory Protein (RKIP) Binding Pocket: NMR-Based Screening Identifies Small-Molecule Ligands

Raf kinase inhibitory protein (RKIP), also known as phoshaptidylethanolamine binding protein (PEBP), has been shown to inhibit Raf and thereby negatively regulate growth factor signaling by the Raf/MAP kinase pathway. RKIP has also been shown to suppress metastasis. We have previously demonstrated that RKIP/Raf interaction is regulated by two mechanisms: phosphorylation of RKIP at Ser-153, and occupation of RKIP's conserved ligand binding domain with a phospholipid (2-dihexanoyl-sn-glycero-3-phosphoethanolamine; DHPE). In addition to phospholipids, other ligands have been reported to bind this domain; however their binding properties remain uncharacterized.In this study, we used high-resolution heteronuclear NMR spectroscopy to screen a chemical library and assay a number of potential RKIP ligands for binding to the protein. Surprisingly, many compounds previously postulated as RKIP ligands showed no detectable binding in near-physiological solution conditions even at millimolar concentrations. In contrast, we found three novel ligands for RKIP that specifically bind to the RKIP pocket. Interestingly, unlike the phospholipid, DHPE, these newly identified ligands did not affect RKIP binding to Raf-1 or RKIP phosphorylation. One out of the three ligands displayed off target biological effects, impairing EGF-induced MAPK and metabolic activity.This work defines the binding properties of RKIP ligands under near physiological conditions, establishing RKIP's affinity for hydrophobic ligands and the importance of bulky aliphatic chains for inhibiting its function. The common structural elements of these compounds defines a minimal requirement for RKIP binding and thus they can be used as lead compounds for future design of RKIP ligands with therapeutic potential

Behavior Responses to Chemical and Optogenetic Stimuli in Drosophila Larvae

An animal’s ability to navigate an olfactory environment is critically dependent on the activities of its first-order olfactory receptor neurons (ORNs). While considerable research has focused on ORN responses to odorants, the mechanisms by which olfactory information is encoded in the activities of ORNs and translated into navigational behavior remain poorly understood. We sought to determine the contributions of most Drosophila melanogaster larval ORNs to navigational behavior. Using odorants to activate ORNs and a larval tracking assay to measure the corresponding behavioral response, we observed that larval ORN activators cluster into four groups based on the behavior responses elicited from larvae. This is significant because it provides new insights into the functional relationship between ORN activity and behavioral response. Subsequent optogenetic analyses of a subset of ORNs revealed previously undescribed properties of larval ORNs. Furthermore, our results indicated that different temporal patterns of ORN activation elicit different behavioral outputs: some ORNs respond to stimulus increments while others respond to stimulus decrements. These results suggest that the ability of ORNs to encode temporal patterns of stimulation increases the coding capacity of the olfactory circuit. Moreover, the ability of ORNs to sense stimulus increments and decrements facilitates instantaneous evaluations of concentration changes in the environment. Together, these ORN properties enable larvae to efficiently navigate a complex olfactory environment. Ultimately, knowledge of how ORN activity patterns and their weighted contributions influence odor coding may eventually reveal how peripheral information is organized and transmitted to subsequent layers of a neural circuit

A systematic approach towards the identification and protection of vulnerable marine ecosystems

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Marine Policy 49 (2014):146-154, doi:10.1016/j.marpol.2013.11.017.The United Nations General Assembly in 2006 and 2009 adopted resolutions that call for the identification and protection of vulnerable marine ecosystems (VMEs) from significant adverse impacts of bottom fishing. While general criteria have been produced, there are no guidelines or protocols that elaborate on the process from initial identification through to the protection of VMEs. Here, based upon an expert review of existing practices, a 10-step framework is proposed: 1) Comparatively assess potential VME indicator taxa and habitats in a region; 2) determine VME thresholds; 3) consider areas already known for their ecological importance; 4) compile information on the distributions of likely VME taxa and habitats, as well as related environmental data; 5) develop predictive distribution models for VME indicator taxa and habitats; 6) compile known or likely fishing impacts; 7) produce a predicted VME naturalness distribution (areas of low cumulative impacts); 8) identify areas of higher value to user groups; 9) conduct management strategy evaluations to produce trade-off scenarios; 10) review and re-iterate, until spatial management scenarios are developed that fulfil international obligations and regional conservation and management objectives. To date, regional progress has been piecemeal and incremental. The proposed 10-step framework combines these various experiences into a systematic approach.The New Zealand Ministry of Science and Innovation (now known as the Ministry of Business, Innovation and Employment) provided funding for the worksho

Taphonomic and zooarchaeological investigations at the middle Pleistocene site of Ti's al Ghadah, western Nefud Desert, Saudi Arabia

In recent years, the Arabian Peninsula has emerged as a key region for elucidating hominin and faunal evolution and dispersals between Africa and Eurasia. Central to this research is the middle Pleistocene site of Ti's al Ghadah (TAG) which has yielded a diverse and abundant fossil faunal assemblage and the earliest chronometrically dated evidence for hominins in this part of the world. Here, we present the first detailed taphonomic study of the large Unit 5 fossil assemblage from the site. We aim to assess which actor/s were responsible for the accumulation of the assemblage and evaluate evidence that might be consistent with the accumulation of fauna by hominins. We also describe, for the first time, fossils and lithic artefacts from stratigraphic horizons not previously considered, providing taphonomic insights into their accumulation. The taphonomic work shows that the Unit 5 faunal assemblage was accumulated by ambush predators, likely large felids and hominins, in a lake side environment, and that carcasses were subsequently scavenged by more durophagus carnivores such as hyenas and canids. Less can be reliably said regarding the newly described fossil assemblages given their poor preservation and significant wind abrasion, but large carnivores again appear to have played a role, and hominins probably played a role in the accumulation of at least one of these. This study provides the first detail insights into the interplay between hominins, carnivores, and herbivores in Arabia, and suggests that watering holes have been a focus on the Arabian landscape for resources since the middle Pleistocene

First evidence for human occupation of a lava tube in Arabia: The archaeology of Umm Jirsan Cave and its surroundings, northern Saudi Arabia

Recent advances in interdisciplinary archaeological research in Arabia have focused on the evolution and historical development of regional human populations as well as the diverse patterns of cultural change, migration, and adaptations to environmental fluctuations. Obtaining a comprehensive understanding of cultural developments such as the emergence and lifeways of Neolithic groups has been hindered by the limited preservation of stratified archaeological assemblages and organic remains, a common challenge in arid environments. Underground settings like caves and lava tubes, which are prevalent in Arabia but which have seen limited scientific exploration, offer promising opportunities for addressing these issues. Here, we report on an archaeological excavation and a related survey at and around Umm Jirsan lava tube in the Harrat Khaybar, north-western Saudi Arabia. Our results reveal repeated phases of human occupation of the site ranging from at least the Neolithic through to the Chalcolithic/Bronze Age. Pastoralist use of the lava tube and surrounding landscape is attested in rock art and faunal records, suggesting that Umm Jirsan was situated along a pastoral route linking key oases. Isotopic data indicates that herbivores primarily grazed on wild grasses and shrubs rather than being provided with fodder, while humans had a diet consistently high in protein but with increasing consumption of C3 plants through-time, perhaps related to the emergence of oasis agriculture. While underground and naturally sheltered localities are globally prominent in archaeology and Quaternary science, our work represents the first such combined records for Saudi Arabia and highlight the potential for interdisciplinary studies in caves and lava tubes

Outcome of COVID-19 in hospitalised immunocompromised patients:An analysis of the WHO ISARIC CCP-UK prospective cohort study

Background: Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic. Methods and findings: We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. Approximately 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI [0.7, 0.85], p < 0.001) or ventilation (adjusted OR 0.65, 95% CI [0.56, 0.76], p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI [1.87, 2.15], p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent. Conclusions: Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group. Trial registration: ISRCTN 66726260

iPSC-Derived Dopamine Neurons Reveal Differences between Monozygotic Twins Discordant for Parkinson’s Disease

SummaryParkinson’s disease (PD) has been attributed to a combination of genetic and nongenetic factors. We studied a set of monozygotic twins harboring the heterozygous glucocerebrosidase mutation (GBA N370S) but clinically discordant for PD. We applied induced pluripotent stem cell (iPSC) technology for PD disease modeling using the twins’ fibroblasts to evaluate and dissect the genetic and nongenetic contributions. Utilizing fluorescence-activated cell sorting, we obtained a homogenous population of “footprint-free” iPSC-derived midbrain dopaminergic (mDA) neurons. The mDA neurons from both twins had ∼50% GBA enzymatic activity, ∼3-fold elevated α-synuclein protein levels, and a reduced capacity to synthesize and release dopamine. Interestingly, the affected twin’s neurons showed an even lower dopamine level, increased monoamine oxidase B (MAO-B) expression, and impaired intrinsic network activity. Overexpression of wild-type GBA and treatment with MAO-B inhibitors normalized α-synuclein and dopamine levels, suggesting a combination therapy for the affected twin