Stable hZW10 kinetochore residency, mediated by hZwint-1 interaction, is essential for the mitotic checkpoint

The mitotic checkpoint is an essential surveillance mechanism that ensures high fidelity chromosome segregation during mitosis. Mitotic checkpoint function depends on numerous kinetochore proteins, including ZW10, ROD, and Zwilch (the ROD–ZW10–Zwilch complex). Through an extensive mutagenesis screen of hZW10, we have mapped the kinetochore localization domain of hZW10 as well as the hZwint-1 interaction domain. We find that hZwint-1–noninteracting mutants still localize to kinetochores. In addition, using fluorescence recovery after photobleaching, we have found that hZW10 residency at metaphase kinetochores is brief (half-time of 13 s). However, during prometaphase or at unattached kinetochores, enhanced green fluorescent protein–hZW10 becomes a stable component of the kinetochore. Moreover, we find that stable hZW10 kinetochore residency at prometaphase kinetochores is dependent on its interaction with hZwint-1, and is essential for mitotic checkpoint arrest

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Magnetic ordering of Mn sublattice, dense Kondo lattice behavior of Ce in (RPd3)8Mn (R = La, Ce)

We have synthesized two new interstitial compounds (RPd3)8Mn (R = La and Ce). The Mn ions present in "dilute" concentration of just 3 molar percent form a sublattice with an unusually large Mn-Mn near neighbor distance of ~ 85 nm. While the existence of (RPd3)8M (where M is a p-block element) is already documented in the literature, the present work reports for the first time the formation of this phase with M being a 3d element. In (LaPd3)8Mn, the Mn sub-lattice orders antiferromagnetically as inferred from the peaks in low-field magnetization at 48 K and 23 K. The latter peak progressively shifts towards lower temperatures in increasing magnetic field and disappears below 1.8 K in a field of ~ 8 kOe. On the other hand in (CePd3)8Mn the Mn sublattice undergoes a ferromagnetic transition around 35 K. The Ce ions form a dense Kondo-lattice and are in a paramagnetic state at least down to 1.5 K. A strongly correlated electronic ground state arising from Kondo effect is inferred from the large extrapolated value of C/T = 275 mJ/Ce-mol K^2 at T = 0 K. In contrast, the interstitial alloys RPd3Mnx (x = 0.03 and 0.06), also synthesized for the first time, have a spin glass ground state due to the random distribution of the Mn ions over the available "1b" sites in the parent RPd3 crystal lattice.Comment: 18 figures and 20 pages of text documen

Deprivation is associated with anxiety and stress. A population-based longitudinal household survey among Chinese adults in Hong Kong

BACKGROUND: Mental illness is a major disease burden in the world and disproportionately affects the socially disadvantaged, but studies on the longitudinal association of poverty with anxiety and stress are rare, especially in Asia. Using data from Hong Kong, we aimed to (1) assess the cross-sectional association of poverty with anxiety and stress at baseline, and (2) to examine whether baseline poverty and change in poverty status over time are associated with a subsequent change in anxiety and stress. METHODS: Data were obtained from two waves of a territory-wide longitudinal survey in Hong Kong, with sample sizes of n=1970 and n=1224 for baseline and follow-up, respectively. Poverty was measured with a Deprivation Index and income-poverty. Anxiety and stress symptoms were assessed using Chinese Depression, Anxiety and Stress Scale-21 Items. We conducted cross-sectional and longitudinal analyses on the association of poverty with anxiety and stress. OUTCOMES: Deprivation, but not income-poverty, was significantly associated with both outcomes at baseline. Increased deprivation over time was associated with greater score and increased risk of anxiety and stress. Persistent deprivation over time was associated with greater anxiety and stress, and increased risk of incident anxiety. INTERPRETATION: Deprivation could have significant independent effects on anxiety and stress, even after adjusting for the effects of income-poverty. Greater attention should be paid to deprivation in policymaking to tackle the inequalities of mental health problems, especially since stress and anxiety are precursors to more severe forms of mental illness and other comorbidities

Impact of rural-to-urban migration on family and gender values in China

Drawing on data from the 2006 China General Social Survey, propensity score matching was used to investigate the impact of rural-to-urban migration on family and gender values in China at distinct stages of the migratory process. Little evidence of ideational difference is found between rural natives who intend to migrate to urban areas and those who intend to stay in rural China. However, rural-to-urban migration has significant, diverse and gendered impacts on various domains of family and gender values at distinct migratory stages. The results also cast light on the important roles played by hukou status and various forms of socioeconomic and cultural status, such as education and occupation, in mediating the impact of rural-to-urban migration on family and gender values. The ideational impact of migration is shown to be shaped by China’s distinctive institutional features

Micellular fluorescence resonance energy transfer based fluorescent ratiometric response to hydrocarbon analytes

Fluorescence resonance energy transfer (FRET) has been utilised to develop numerous selective and sensitive fluorescent ratiometric sensors. Typically, FRET-based fluorescent ratiometric sensors rely on chemical interactions between the sensor and analyte to illicit a response, thus unreactive hydrocarbons are a neglected analyte and a source for new sensors. By containing an unbound donor–acceptor system within micelles, energy transfer is enabled by spatial confinement. This offers the potential of a ratiometric response as a hydrocarbon analyte is added. Introducing a hydrocarbon analyte to this system causes micelles to swell, increasing the donor–acceptor distance and thus reducing the amount of observed energy transfer. We present InP/ZnS quantum dot donors interacting with a Nile Red acceptor, confined by cetyltrimethylammonium bromide (CTAB)-based micelles. We alleviated spatial confinement of the pair within micelles using common laboratory solvents to represent hydrocarbons, (toluene, hexane and octadecene). We constructed calibration curves for each solvent and found effective sensing ranges of 0.009–0.21, 0.008–0.27 and 0.003–0.06 M for toluene, hexane and octadecene, respectively. This study contributes towards the development of new hydrocarbon sensors utilising this new mechanism

Antimicrobial susceptibility of bacteria isolated from newborns with suspected or confirmed necrotising enterocolitis

Aim. This audit aimed to identify which bacteria were associated with necrotising enterocolitis (NEC) and determine their antibiotic sensitivities. Methods. A retrospective audit of all infants with a diagnosis of suspected NEC or confirmed NEC and a positive culture (blood/faeces/operative specimen or vascular access device) between January 2000 and September 2007 was performed. Results. Ninety nine infants had a diagnosis of suspected (45) or confirmed NEC (54). Seventeen patients had suspected (5) or confirmed (12) NEC and a positive culture result. 12 babies had positive blood cultures associated with their NEC. Only 4 of the 12 cases of NEC with a positive blood culture received adequate first line cover for their subsequently identified infecting organism. Conclusions. Due to the limitations of this study we are unable to make general recommendations on the first line antibiotic choice for babies with suspected or confirmed NEC. Our current regime of Ampicillin, Gentamicin and Metronidazole failed to adequately treat 8 of the 12 organisms subsequently isolated in blood cultures. Only the combination of Vancomycin and Meropenem would have adequately treated all the bacteria identified. The concern with this approach is the possible emergence of multi drug resistant bacteria

Structure optimization in an off-lattice protein model

We study an off-lattice protein toy model with two species of monomers interacting through modified Lennard-Jones interactions. Low energy configurations are optimized using the pruned-enriched-Rosenbluth method (PERM), hitherto employed to native state searches only for off lattice models. For 2 dimensions we found states with lower energy than previously proposed putative ground states, for all chain lengths $\ge 13$. This indicates that PERM has the potential to produce native states also for more realistic protein models. For $d=3$, where no published ground states exist, we present some putative lowest energy states for future comparison with other methods.Comment: 4 pages, 2 figure

Challenges and solutions to cancer-related financial toxicity according to Australian health professionals: qualitative results from a national survey

Purpose: To qualitatively explore Australian healthcare professionals’ perspectives on how to improve the care and management of cancer-related financial toxicity, including relevant practices, services, and unmet needs. Methods: We invited healthcare professionals (HCP) who currently provide care to people with cancer within their role to complete an online survey, which was distributed via the networks of Australian clinical oncology professional associations/organisations. The survey was developed by the Clinical Oncology Society of Australia’s Financial Toxicity Working Group and contained 12 open-ended items which we analysed using descriptive content analysis and NVivo software. Results: HCPs (n = 277) believed that identifying and addressing financial concerns within routine cancer care was important and most believed this to be the responsibility of all HCP involved in the patient’s care. However, financial toxicity was viewed as a “blind spot” within a medical model of healthcare, with a lack of services, resources, and training identified as barriers to care. Social workers reported assessment and advocacy were part of their role, but many reported lacking formal training and understanding of financial complexities/laws. HCPs reported positive attitudes towards transparent discussions of costs and actioning cost-reduction strategies within their control, but feelings of helplessness when they perceived no solution was available. Conclusion: Identifying financial needs and providing transparent information about cancer-related costs was viewed as a cross-disciplinary responsibility, however, a lack of training and services limited the provision of support. Increased cancer-specific financial counselling and advocacy, via dedicated roles or developing HCPs’ skills, is urgently needed within the healthcare system