The Nuclear Localization of γ-Tubulin Is Regulated by SadB-mediated Phosphorylation

γ-Tubulin is an important cell division regulator that arranges microtubule assembly and mitotic spindle formation. Cytosolic γ-tubulin nucleates α- and β-tubulin in a growing microtubule by forming the ring-shaped protein complex γTuRC. Nuclear γ-tubulin also regulates S-phase progression by moderating the activities of E2 promoter-binding factors. The mechanism that regulates localization of γ-tubulin is currently unknown. Here, we demonstrate that the human Ser/Thr kinase SadB short localizes to chromatin and centrosomes. We found that SadB-mediated phosphorylation of γ-tubulin on Ser³⁸⁵ formed chromatin-associated γ-tubulin complexes that moderate gene expression. In this way, the C-terminal region of γ-tubulin regulates S-phase progression. In addition, chromatin levels of γ-tubulin were decreased by the reduction of SadB levels or expression of a non-phosphorylatable Ala³⁸⁵-γ-tubulin but were enhanced by expression of SadB, wild-type γ-tubulin, or a phosphomimetic Asp³⁸⁵-γ-tubulin mutant. Our results demonstrate that SadB kinases regulate the cellular localization of γ-tubulin and thereby control S-phase progression.     

Recording of Influenza-Like Illness in UK Primary Care 1995-2013: Cohort Study

Background

There is a lack of recent studies examining recording of influenza-like illness (ILI) in primary care in the UK over time and according to population characteristics. Our aim was to determine time trends and socio-demographic patterns of ILI recorded consultations in primary care.

Methods

We used The Health Improvement Network (THIN) UK primary care database and extracted data on all ILI consultations between 1995 and 2013. We estimated ILI recorded consultation rates per 100,000 person-weeks (pw) by age, gender, deprivation and winter season. Negative binomial regression models were used to examine time trends and the effect of socio-demographic characteristics. Trends in ILI recorded consultations were compared to trends in consultations with less specific symptoms (cough or fever) recorded.

Results

The study involved 7,682,908 individuals in 542 general practices. The ILI consultation rate decreased from 32.5/100,000 pw (95% confidence interval (CI) 32.1, 32.9) in 1995–98 to 15.5/100,000 pw (95% CI 15.4, 15.7) by 2010–13. The decrease occurred prior to 2002/3, and rates have remained largely stable since then. Declines were evident in all age groups. In comparison, cough or fever consultation rates increased from 169.4/100,000 pw (95% CI 168.6, 170.3) in 1995–98 to 237.7/100,000 pw (95% CI 237.2, 238.2) in 2010–13. ILI consultation rates were highest among individuals aged 15–44 years, higher in women than men, and in individuals from deprived areas.

Conclusion

There is substantial variation in ILI recorded consultations over time and by population socio-demographic characteristics, most likely reflecting changing recording behaviour by GPs. These results highlight the difficulties in using coded information from electronic primary care records to measure the severity of influenza epidemics across time and assess the relative burden of ILI in different population subgroups.     

National Survey of Radiation Dose and Image Quality in Adult CT Head Scans in Taiwan

Introduction

The purpose of the present study was to evaluate the influence of different variables on radiation dose and image quality based on a national database.

Materials and Methods

Taiwan’s Ministry of Health and Welfare requested all radiology departments to complete a questionnaire for each of their CT scanners. Information gathered included all scanning parameters for CT head scans. For the present analysis, CT machines were divided into three subgroups: single slice CT (Group A); multi-detector CT (MDCT) with 2-64 slices (Group B); and MDCT with more than 64 slices (Group C). Correlations between computed tomography dose index (CTDI) and signal-to-noise ratio (SNR) with cumulated tube rotation number (CTW(n)) and cumulated tube rotation time (CTW(s)), and sub group analyses of CTDI and SNR across the three groups were performed.

Results

CTDI values demonstrated a weak correlation (r = 0.33) with CTW(n) in Group A. SNR values demonstrated a weak negative correlation (r = -0.46) with CTW(n) in Group C. MDCT with higher slice numbers used more tube potential resulting in higher effective doses. There were both significantly lower CTDI and SNR values in helical mode than in axial mode in Group B, but not Group C.

Conclusion

CTW(n) and CTW(s) did not influence radiation output. Helical mode is more often used in MDCT and results in both lower CTDI and SNR compared to axial mode in MDCT with less than 64 slices.     

Factors Impacting Transgender Patients’ Discomfort with Their Family Physicians: A Respondent-Driven Sampling Survey

Background

Representing approximately 0.5% of the population, transgender (trans) persons in Canada depend on family physicians for both general and transition-related care. However, physicians receive little to no training on this patient population, and trans patients are often profoundly uncomfortable and may avoid health care. This study examined factors associated with patient discomfort discussing trans health issues with a family physician in Ontario, Canada.

Methods

433 trans people age 16 and over were surveyed using respondent-driven sampling for the Trans PULSE Project; 356 had a family physician. Weighted logistic regression models were fit to produce prevalence risk ratios (PRRs) via average marginal predictions, for transmasculine (n = 184) and transfeminine (n = 172) trans persons.

Results

Among the 83.1% (95% CI = 77.4, 88.9) of trans Ontarians who had a family physician, approximately half reported discomfort discussing trans health issues. 37.2% of transmasculine and 38.1% of transfeminine persons reported at least one trans-specific negative experience. In unadjusted analysis, sociodemographics did not predict discomfort, but those who planned to medically transition sex, but had not begun, were more likely to report discomfort (transmasculine: PRR = 2.62 (95% CI = 1.44, 4.77); transfeminine: PRR = 1.85 (95% CI = 1.08, 3.15)). Adjusted for other factors, greater perceived physician knowledge about trans issues was associated with reduced likelihood of discomfort, and previous trans-specific negative experiences with a family physician with increased discomfort. Transfeminine persons who reported three or more types of negative experiences were 2.26 times as likely, and transmasculine persons 1.61 times as likely, to report discomfort. In adjusted analyses, sociodemographic associations differed by gender, with being previously married or having higher education associated with increased risk of discomfort among transfeminine persons, but decreased risk among transmasculine persons.

Conclusions

Within this transgender population, discomfort in discussing trans health issues with a family physician was common, presenting a barrier to accessing primary care despite having a regular family physician and “universal” health insurance.     

Molecular detection of intra-population structure in a threatened potoroid,Potorous tridactylus: conservation management and sampling implications

Fine-scale genetic structure was investigated in three regional populations of the long-nosed potoroo (Potorous tridactylus) a threatened endemic marsupial. Two populations were from the Australian mainland and one from an island. Populations were sub-sampled at two sites, 6–8 km apart, connected by suitable habitat for dispersal. Factors influencing fine-scale structure were investigated by genotyping 157 individuals at 10 microsatellite loci and sequencing a ~621 bp region of the mtDNA control region. Results indicated that P. tridactylus populations exhibit significant intra-population structure, with significant F _ST and Φ _ST values recorded between subpopulations. This structure appeared mediated by small neighbourhood size, female philopatry and limited dispersal over 6–8 km, predominantly by males. Results highlighted several important features of P. tridactylus populations that have implications for conservation. Firstly, the small neighbourhood size suggests any investigations of intra-population structure should be conducted on a finer scale (e.g. 25–50 m) than many current monitoring programs. Secondly, the island populations were genetically depauperate, which may reflect processes occurring in many isolated ‘mainland island’ populations. Thirdly, the lower gene flow identified between populations separated by anthropogenically modified habitat suggests P. tridactylus is sensitive to changes in habitat configuration.     

Modulation ofTcf7l2 expression alters behavior in mice

The comorbidity of type 2 diabetes (T2D) with several psychiatric diseases is well established. While environmental factors may partially account for these co-occurrences, common genetic susceptibilities could also be implicated in the confluence of these diseases. In support of shared genetic burdens, TCF7L2, the strongest genetic determinant for T2D risk in the human population, has been recently implicated in schizophrenia (SCZ) risk, suggesting that this may be one of many loci that pleiotropically influence both diseases. To investigate whether Tcf7l2 is involved in behavioral phenotypes in addition to its roles in glucose metabolism, we conducted several behavioral tests in mice with null alleles of Tcf7l2 or overexpressing Tcf7l2. We identified a role for Tcf7l2 in anxiety-like behavior and a dose-dependent effect of Tcf7l2 alleles on fear learning. None of the mutant mice showed differences in prepulse inhibition (PPI), which is a well-established endophenotype for SCZ. These results show that Tcf7l2 alters behavior in mice. Importantly, these differences are observed prior to the onset of detectable glucose metabolism abnormalities. Whether these differences are related to human anxiety-disorders or schizophrenia remains to be determined. These animal models have the potential to elucidate the molecular basis of psychiatric comorbidities in diabetes and should therefore be studied further.     

The Sea Peoples, from cuneiform tablets to carbon dating

The 13(th) century BC witnessed the zenith of the Aegean and Eastern Mediterranean civilizations which declined at the end of the Bronze Age, ～3200 years ago. Weakening of this ancient flourishing Mediterranean world shifted the political and economic centres of gravity away from the Levant towards Classical Greece and Rome, and led, in the long term, to the emergence of the modern western civilizations. Textual evidence from cuneiform tablets and Egyptian reliefs from the New Kingdom relate that seafaring tribes, the Sea Peoples, were the final catalyst that put the fall of cities and states in motion. However, the lack of a stratified radiocarbon-based archaeology for the Sea People event has led to a floating historical chronology derived from a variety of sources spanning dispersed areas. Here, we report a stratified radiocarbon-based archaeology with anchor points in ancient epigraphic-literary sources, Hittite-Levantine-Egyptian kings and astronomical observations to precisely date the Sea People event. By confronting historical and science-based archaeology, we establish an absolute age range of 1192-1190 BC for terminal destructions and cultural collapse in the northern Levant. This radiocarbon-based archaeology has far-reaching implications for the wider Mediterranean, where an elaborate network of international relations and commercial activities are intertwined with the history of civilizations.     

Growth anomalies on the coral genera Acropora and Porites are strongly associated with host density and human population size across the Indo-Pacific

Growth anomalies (GAs) are common, tumor-like diseases that can cause significant morbidity and decreased fecundity in the major Indo-Pacific reef-building coral genera, Acropora and Porites. GAs are unusually tractable for testing hypotheses about drivers of coral disease because of their pan-Pacific distributions, relatively high occurrence, and unambiguous ease of identification. We modeled multiple disease-environment associations that may underlie the prevalence of Acropora growth anomalies (AGA) (n = 304 surveys) and Porites growth anomalies (PGA) (n = 602 surveys) from across the Indo-Pacific. Nine predictor variables were modeled, including coral host abundance, human population size, and sea surface temperature and ultra-violet radiation anomalies. Prevalence of both AGAs and PGAs were strongly host density-dependent. PGAs additionally showed strong positive associations with human population size. Although this association has been widely posited, this is one of the first broad-scale studies unambiguously linking a coral disease with human population size. These results emphasize that individual coral diseases can show relatively distinct patterns of association with environmental predictors, even in similar diseases (growth anomalies) found on different host genera (Acropora vs. Porites). As human densities and environmental degradation increase globally, the prevalence of coral diseases like PGAs could increase accordingly, halted only perhaps by declines in host density below thresholds required for disease establishment.