ResearchPad - 32 https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Cell polarity–dependent centrosome separation in the <i>C. elegans</i> embryo]]> https://www.researchpad.co/article/elastic_article_15326 In animal cells, faithful chromosome segregation depends on the assembly of a bipolar spindle driven by the timely separation of the two centrosomes. Here we took advantage of the highly stereotypical cell divisions in Caenorhabditis elegans embryos to identify new regulators of centrosome separation. We find that at the two-cell stage, the somatic AB cell initiates centrosome separation later than the germline P1 cell. This difference is strongly exacerbated by the depletion of the kinesin-13 KLP-7/MCAK, resulting in incomplete centrosome separation at NEBD in AB but not P1. Our genetic and cell biology data indicate that this phenotype depends on cell polarity via the enrichment in AB of the mitotic kinase PLK-1, which itself limits the cortical localization of the dynein-binding NuMA orthologue LIN-5. We postulate that the timely separation of centrosomes is regulated in a cell type–dependent manner.

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<![CDATA[Lymph Node Imaging in Patients with Primary Breast Cancer: Concurrent Diagnostic Tools]]> https://www.researchpad.co/article/Nb602c4c4-063d-42c6-a392-9bd95fb8407e

Abstract

The detection of lymph node metastasis affects the management of patients with primary breast cancer significantly in terms of staging, treatment, and prognosis. The main goal for the radiologist is to determine and detect the presence of metastatic disease in nonpalpable axillary lymph nodes with a positive predictive value that is high enough to initially select patients for upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with different imaging modalities, but ultrasound is the method of choice for evaluating axillary lymph nodes and for performing image‐guided lymph node interventions. This review aims to provide a comprehensive overview of the available imaging modalities for lymph node assessment in patients diagnosed with primary breast cancer.

Implications for Practice

The detection of lymph node metastasis affects the management of patients with primary breast cancer. The main goal for the radiologist is to detect lymph node metastasis in patients to allow for the selection of patients who should undergo upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with mammography, computed tomography, and magnetic resonance imaging, but ultrasonography is the imaging modality of choice for evaluating axillary lymph nodes. A normal axillary lymph node is characterized by a reniform shape, a maximal cortical thickness of 3 mm without focal bulging, smooth margins, and, depending on size, a discernable central fatty hilum.

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<![CDATA[Body mass index, diet, physical inactivity, and the incidence of dementia in 1 million UK women]]> https://www.researchpad.co/article/Nfcb8d3d1-21de-491a-8874-c3f58b22aaa4

Objective

To help determine whether midlife obesity is a cause of dementia and whether low body mass index (BMI), low caloric intake, and physical inactivity are causes or merely consequences of the gradual onset of dementia by recording these factors early in a large 20-year prospective study and relating them to dementia detection rates separately during follow-up periods of <5, 5 to 9, 10 to 14, and 15+ years.

Methods

A total of 1,136,846 UK women, mean age 56 (SD 5) years, were recruited in 1996 to 2001 and asked about height, weight, caloric intake, and inactivity. They were followed up until 2017 by electronic linkage to National Health Service records, detecting hospital admissions with mention of dementia. Cox regression yielded adjusted rate ratios (RRs) for first dementia detection during particular follow-up periods.

Results

Fifteen years after the baseline survey, only 1% were lost to follow-up, and 89% remained alive with no detected dementia, of whom 18,695 had dementia detected later, at a mean age of 77 (SD 4) years. Dementia detection during years 15+ was associated with baseline obesity (BMI 30+ vs 20–24 kg/m2: RR 1.21, 95% confidence interval 1.16–1.26, p < 0.0001) but not clearly with low BMI, low caloric intake, or inactivity at baseline. The latter 3 factors were associated with increased dementia rates during the first decade, but these associations weakened substantially over time, approaching null after 15 years.

Conclusions

Midlife obesity may well be a cause of dementia. In contrast, behavioral changes due to preclinical disease could largely or wholly account for associations of low BMI, low caloric intake, and inactivity with dementia detection during the first decade of follow-up.

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<![CDATA[Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups]]> https://www.researchpad.co/article/N57dbba97-25a2-45a4-a079-d41dca2e5eb6

Objective

To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium.

Methods

We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis.

Results

In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition.

Conclusions

This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.

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<![CDATA[Hemorrhagic cerebral small vessel disease caused by a novel mutation in 3′ UTR of collagen type IV alpha 1]]> https://www.researchpad.co/article/N6e1389a6-b057-44f9-8aea-3263b2c0f073 ]]> <![CDATA[SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility]]> https://www.researchpad.co/article/Nafa1aa93-c090-4a21-b5c1-05b1bdb45d04

Awadia et al. show that SGEF, a RhoG-specific GEF, forms a ternary complex with two members of the Scribble polarity complex, Scribble and Dlg1, and regulates junction formation, apical contractility, E-cadherin stability, and lumen formation in epithelial cells.

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<![CDATA[Yorkie controls tube length and apical barrier integrity during airway development]]> https://www.researchpad.co/article/N8510fe64-1ef6-4de2-b892-e6d4e824e187

Skouloudaki et al. identify an alternative role of the transcriptional coactivator Yorkie (Yki) in controlling water impermeability and tube size of developing Drosophila airways. Tracheal impermeability is triggered by Yki-mediated transcriptional regulation of δ-aminolevulinate synthase (Alas), whereas tube elongation is controlled by binding of Yki to the actin-severing factor Twinstar.

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<![CDATA[Microtubules promote intercellular contractile force transmission during tissue folding]]> https://www.researchpad.co/article/N2bc9b7b1-9221-4873-aaa4-29095195955f

During morphogenesis, how intercellular contractile force transmission is maintained in the face of tension is not well understood. Ko et al. describe polarized, noncentrosomal microtubules that promote the attachment of actomyosin to cell junctions for proper tissue-wide force integration.

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<![CDATA[M1b Disease in the 8th Edition of TNM Staging of Lung Cancer: Pattern of Single Extrathoracic Metastasis and Clinical Outcome]]> https://www.researchpad.co/article/Nf2f55eb0-3d16-4020-9f4b-a61292f3383b

The 8th edition of TNM staging of lung cancer revised M staging and defined M1b disease with single extrathoracic metastasis, to be distinguished from M1c with multiple extrathoracic metastases in one or more organs. This new distinct category of M1b disease consists of patients with a single extrathoracic metastasis, thus consisting of a strictly defined oligometastatic disease. This article reports the prevalence of M1b disease among patients with stage IV non‐small cell lung cancer, focusing on the clinical characteristics and patterns of single extrathoracic metastasis and relationships with overall survival.

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<![CDATA[Diabetes Mellitus, Hypertension, and Death among 32 Patients with MERS-CoV Infection, Saudi Arabia]]> https://www.researchpad.co/article/N58292302-c1d3-46d0-9614-ccc0e07b6ef4

Diabetes mellitus and hypertension are recognized risk factors for severe clinical outcomes, including death, associated with Middle East respiratory syndrome coronavirus infection. Among 32 virus-infected patients in Saudi Arabia, severity of illness and frequency of death corresponded closely with presence of multiple and more severe underlying conditions.

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<![CDATA[An apicosome initiates self-organizing morphogenesis of human pluripotent stem cells]]> https://www.researchpad.co/article/5c01f916d5eed0c4842bfecb

Establishment of apicobasal polarity is critical for the lumenal epiblast-like morphogenesis of human pluripotent stem cells (hPSC). Taniguchi et al. show that apical polarization begins on the interior of single hPSC, through dynamic formation of a highly organized, apically charged perinuclear complex called the apicosome.

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<![CDATA[Apical polarization and lumenogenesis: The apicosome sheds new light]]> https://www.researchpad.co/article/5c01f923d5eed0c4842c0305

Romero-Morales et al. preview work from the Taniguchi et al. describing the role of a new structure, the apicosome, in lumenogenesis.

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<![CDATA[Membrane curvature directs the localization of Cdc42p to novel foci required for cell–cell fusion]]> https://www.researchpad.co/article/5c01f911d5eed0c4842bfd19

The Rho–GTPase Cdc42p promotes yeast fusion during mating. Smith et al. find that Cdc42p forms a novel focus at the center of the zone of cell fusion that is required for fusion. Formation of the focus depends on fusion proteins and is sensitive to the curvature of the zone of cell fusion.

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