CENP-meta, an essential kinetochore kinesin required for the maintenance of metaphase chromosome alignment in Drosophila.

CENP-meta has been identified as an essential, kinesin-like motor protein in Drosophila. The 257-kD CENP-meta protein is most similar to the vertebrate kinetochore-associated kinesin-like protein CENP-E, and like CENP-E, is shown to be a component of centromeric/kinetochore regions of Drosophila chromosomes. However, unlike CENP-E, which leaves the centromere/kinetochore region at the end of anaphase A, the CENP-meta protein remains associated with the centromeric/kinetochore region of the chromosome during all stages of the Drosophila cell cycle. P-element-mediated disruption of the CENP-meta gene leads to late larval/pupal stage lethality with incomplete chromosome alignment at metaphase. Complete removal of CENP-meta from the female germline leads to lethality in early embryos resulting from defects in metaphase chromosome alignment. Real-time imaging of these mutants with GFP-labeled chromosomes demonstrates that CENP-meta is required for the maintenance of chromosomes at the metaphase plate, demonstrating that the functions required to establish and maintain chromosome congression have distinguishable requirements

Disease associated with equine coronavirus infection and high case fatality rate.

BackgroundEquine coronavirus (ECoV) is associated with clinical disease in adult horses. Outbreaks are associated with a low case fatality rate and a small number of animals with signs of encephalopathic disease are described.ObjectivesThe aim of this study is to describe the epidemiological and clinical features of two outbreaks of ECoV infection that were associated with an high case fatality rate.Animals14 miniature horses and 1 miniature donkey testing fecal positive for ECoV from two related disease outbreaks.MethodsRetrospective study describing the epidemiological findings, clinicopathological findings, and fecal viral load from affected horses.ResultsIn EcoV positive horses, 27% (4/15) of the animals died or were euthanized. Severe hyperammonemia (677 μmol/L, reference range ≤ 60 μmol/L) was identified in one animal with signs of encephalopathic disease that subsequently died. Fecal viral load (ECoV genome equivalents per gram of feces) was significantly higher in the nonsurvivors compared to animals that survived (P = .02).Conclusions and clinical importanceEquine coronavirus had a higher case fatality rate in this group of miniature horses than previously reported in other outbreaks of varying breeds. Hyperammonemia could contribute to signs of encephalopathic disease, and the fecal viral load might be of prognostic value in affected horses

Two Glycerol-3-Phosphate Dehydrogenases from Chlamydomonas have Distinct Roles in Lipid Metabolism.

The metabolism of glycerol-3-phosphate (G3P) is important for environmental stress responses by eukaryotic microalgae. G3P is an essential precursor for glycerolipid synthesis and the accumulation of triacylglycerol (TAG) in response to nutrient starvation. G3P dehydrogenase (GPDH) mediates G3P synthesis but the roles of specific GPDH isoforms are currently poorly understood. Of the five GPDH enzymes in the model alga Chlamydomonas reinhardtii, GPD2 and GPD3 were shown to be induced by nutrient starvation and/or salt stress. Heterologous expression of GPD2, a putative chloroplastic GPDH, and GPD3, a putative cytosolic GPDH, in a yeast gpd1Δ mutant demonstrated functionality of both enzymes. C. reinhardtii knockdown mutants for GPD2 and GPD3 showed no difference in growth but displayed significant reduction in TAG concentration compared to wild type in response to phosphorus or nitrogen starvation. Overexpression of GPD2 and GPD3 in C. reinhardtii gave distinct phenotypes. GPD2 overexpression lines showed only subtle metabolic phenotypes and no significant alteration in growth. In contrast, GPD3 overexpression lines displayed significantly inhibited growth and chlorophyll concentration, reduced glycerol concentration, and changes to lipid composition compared to wild type, including increased abundance of phosphatidic acids but reduced abundance of diglycerides, triglycerides and phosphatidylglycerol lipids. This may indicate a block in the downstream glycerolipid metabolism pathway in GPD3 overexpression lines. Thus, lipid engineering by GPDH modification may depend on the activities of other downstream enzyme steps. These results also suggest that GPD2 and GPD3 GPDH isoforms are important for nutrient starvation-induced TAG accumulation but have distinct metabolic functions

Characterization of kinetic and kinematic parameters for wearable robotics

The design process of a wearable robotic device for human assistance requires the characterization of both kinetic and kinematic parameters (KKP) of the human joints. The first step in this process is to extract the KKP from different gait analyses studies. This work is based on the human lower limb considering the following activities of daily living (ADL): walking over ground, stairs ascending/descending, ramp ascending/descending and chair standing up. The usage of different gait analyses in the characterization process, causes the data to have great variations from one study to another. Therefore, the data is graphically represented using Matlab® and Excel® to facilitate its assessment. Finally, the characterization of the KKP performed was proved to be useful in assessing the data reliability by directly comparing all the studies between each other; providing guidelines for the selection of actuator capacities depending on the end application; and highlighting optimization opportunities such as the implementation of agonist-antagonist actuators for particular human joints

Is dietary pattern of schizophrenia patients different from healthy subjects?

<p>Abstract</p> <p>Background</p> <p>There are limited findings about dietary patterns and food preferences among patients suffering from schizophrenia. The main objective of this study was therefore to compare the nutritional pattern of schizophrenia patients with that of matched healthy subjects.</p> <p>Methods</p> <p>The dietary pattern of 30 hospitalized 16–67 years old schizophrenic patients (11 female) was compared with that of 30 healthy age and sex matched individuals as control group. Subjects' anthropometric measurements including weight, height and body mass index (BMI), semi-quantitative food frequency (FFQ), medical and food history questionnaires were also collected and FFQs were then scored using Food Guide Pyramid to obtain the dietary scores. Percent body fat (%BF) was measured using bioelectrical impedance analysis (BIA) method.</p> <p>Results</p> <p>Female patients had more %BF and lower dietary pattern scores than that of their controls (32 ± 3.6 vs 27.7 ± 4.6 percent and 43.2 ± 11.9 vs 54.5 ± 10.7 points; respectively, p < 0.05 for both). They also consumed less milk and dairy products, fresh vegetables, fruits, chicken, and nuts compared with the female controls (p < 0.03). However, these patients used to eat more full-fat cream and carbonated drinks (p < 0.05). Male patients had lower BMI (22 ± 4.7 vs 25.6 ± 4.4; p < 0.05) than their counterpart controls but there was no significant difference between their %BFs. Moreover, they used to have more full-fat cream, hydrogenated fats, less red meat and nuts compared with the male controls (p < 0.05).</p> <p>Conclusion</p> <p>Schizophrenia patients have poor nutritional patterns. In particular, female patients have more percent body fat and lower dietary pattern scores compared with their healthy controls. All patients used to consume more fats and sweet drinks frequently. The findings of this study suggest that schizophrenia patients need specific medical nutrition therapies through limiting dietary fats and sugars intakes and weight control. Whether obesity is the consequence of disease, dietary preference or medications used remains to be cleared.</p

Grey matter changes can improve the prediction of schizophrenia in subjects at high risk

BACKGROUND: We hypothesised that subjects at familial high risk of developing schizophrenia would have a reduction over time in grey matter, particularly in the temporal lobes, and that this reduction may predict schizophrenia better than clinical measurements. METHODS: We analysed magnetic resonance images of 65 high-risk subjects from the Edinburgh High Risk Study sample who had two scans a mean of 1.52 years apart. Eight of these 65 subjects went on to develop schizophrenia an average of 2.3 years after their first scan. RESULTS: Changes over time in the inferior temporal gyrus gave a 60% positive predictive value (likelihood ratio >10) of developing schizophrenia compared to the overall 13% risk in the cohort as a whole. CONCLUSION: Changes in grey matter could be used as part of a predictive test for schizophrenia in people at enhanced risk for familial reasons, particularly for positive predictive power, in combination with other clinical and cognitive predictive measures, several of which are strong negative predictors. However, because of the limited number of subjects, this test requires independent replication to confirm its validity

The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making.

BACKGROUND: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. METHODS: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. RESULTS: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5-60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0-25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. DISCUSSION: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes

Task-Related Effects on the Temporal and Spatial Dynamics of Resting-State Functional Connectivity in the Default Network

Recent evidence points to two potentially fundamental aspects of the default network (DN), which have been relatively understudied. One is the temporal nature of the functional interactions among nodes of the network in the resting-state, usually assumed to be static. The second is possible influences of previous brain states on the spatial patterns (i.e., the brain regions involved) of functional connectivity (FC) in the DN at rest. The goal of the current study was to investigate modulations in both the spatial and temporal domains. We compared the resting-state FC of the DN in two runs that were separated by a 45 minute interval containing cognitive task execution. We used partial least squares (PLS), which allowed us to identify FC spatiotemporal patterns in the two runs and to determine differences between them. Our results revealed two primary modes of FC, assessed using a posterior cingulate seed – a robust correlation among DN regions that is stable both spatially and temporally, and a second pattern that is reduced in spatial extent and more variable temporally after cognitive tasks, showing switching between connectivity with certain DN regions and connectivity with other areas, including some task-related regions. Therefore, the DN seems to exhibit two simultaneous FC dynamics at rest. The first is spatially invariant and insensitive to previous brain states, suggesting that the DN maintains some temporally stable functional connections. The second dynamic is more variable and is seen more strongly when the resting-state follows a period of task execution, suggesting an after-effect of the cognitive activity engaged during task that carries over into resting-state periods

The elusive archaeology of Kongo urbanism: the case of Kindoki, Mbanza Nsundi (Lower Congo, DRC)

We present here results, analyses and an in-depth historical contextualisation of the fieldwork undertaken in 2012 and 2013 at the Kindoki site in the Lower Congo (DRC). This site is linked with Mbanza Nsundi, one of the Kongo Kingdom's provincial capitals, which turns out to be archaeologically 'elusive'. Pinpointing its location proved to be particularly challenging. To this end, a historically-informed excavation methodology was developed that was never implemented in Central Africa before. We combined a strategy of systematic test pits with a large-scale 50 m grid approach. A cemetery was identified on Kindoki Hill with distinct but contemporaneous quarters of a 16th-17thcenturies settlement on both sides. The cemetery itself contains mainly 18th-century burials, in all likelihood of successive Nsundi rulers. The foreign, especially Portuguese, ceramics excavated on the hilltop and the hundreds of Venetian and likely Bavarian beads found in the graves are indicative of Mbanza Nsundi's connection to trade routes linking the Atlantic coast with the Pool region. The most striking discovery is that of a previously unknown type of comb-impressed pottery, from a pit with a calibrated radiocarbon date AD 1294-1393 (2 sigma). This suggests that a settlement had been developing at Kindoki since at least the 14th century, which allows us, for the very first time, to spatially bridge Kongo history and 'prehistory'. For the entire Lower Congo region only three 14C dates posterior to AD 1000 were available before the start of the KongoKing project, twelve have been added for just Kindoki

Assessing harmful effects in systematic reviews.

BACKGROUND: Balanced decisions about health care interventions require reliable evidence on harms as well as benefits. Most systematic reviews focus on efficacy and randomised trials, for which the methodology is well established. Methods to systematically review harmful effects are less well developed and there are few sources of guidance for researchers. We present our own recent experience of conducting systematic reviews of harmful effects and make suggestions for future practice and further research. METHODS: We described and compared the methods used in three systematic reviews. Our evaluation focused on the review question, study designs and quality assessment. RESULTS: One review question focused on providing information on specific harmful effects to furnish an economic model, the other two addressed much broader questions. All three reviews included randomised and observational data, although each defined the inclusion criteria differently. Standard methods were used to assess study quality. Various practical problems were encountered in applying the study design inclusion criteria and assessing quality, mainly because of poor study design, inadequate reporting and the limitations of existing tools. All three reviews generated a large volume of work that did not yield much useful information for health care decision makers. The key areas for improvement we identified were focusing the review question and developing methods for quality assessment of studies of harmful effects. CONCLUSIONS: Systematic reviews of harmful effects are more likely to yield information pertinent to clinical decision-making if they address a focused question. This will enable clear decisions to be made about the type of research to include in the review. The methodology for assessing the quality of harmful effects data in systematic reviews requires further development