Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery

BACKGROUND: Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified. RESULTS: To search for such proteins twenty three nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells. CONCLUSIONS: The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning.Publisher PDFPeer reviewe

Geophagy Practices and the Content of Chemical Elements in the Soil Eaten by Pregnant Women in Artisanal and Small Scale Gold Mining Communities in Tanzania.

Geophagy, a form of pica, is the deliberate consumption of soil and is relatively common across Sub-Saharan Africa. In Tanzania, pregnant women commonly eat soil sticks sold in the market (pemba), soil from walls of houses, termite mounds, and ground soil (kichuguu). The present study examined geophagy practices of pregnant women in a gold mining area of Geita District in northwestern Tanzania, and also examined the potential for exposure to chemical elements by testing soil samples. We conducted a cross sectional study using a convenience sample of 340 pregnant women, ranging in age from 15-49 years, who attended six government antenatal clinics in the Geita District, Tanzania. Structured interviews were conducted in June-August, 2012, to understand geophagy practices. In addition, soil samples taken from sources identified by pregnant women practicing geophagy were analysed for mineral element content. Geophagy was reported by 155 (45.6%) pregnant women with 85 (54.8%) initiating the practice in the first trimester. A total of 101 (65%) pregnant women reported eating soil 2 to 3 times per day while 20 (13%) ate soil more than 3 times per day. Of 155 pregnant women 107 (69%) bought pemba from local shops, while 48 (31%) consumed ground soil kichuguu. The estimated mean quantity of soil consumed from pemba was 62.5 grams/day. Arsenic, chromium, copper, iron, manganese, nickel and zinc levels were found in both pemba and kichuguu samples. Cadmium and mercury were found only in the kichuguu samples. Based on daily intake estimates, arsenic, copper and manganese for kichuguu and copper and manganese for pemba samples exceed the oral Minimum Risk Levels designated by the U.S. Agency for Toxic Substance and Disease Registry. Almost 50% of participants practiced geophagy in Geita District consistent with other reports from Africa. Both pemba and kichuguu contained chemical elements at varying concentration, mostly above MRLs. As such, pregnant women who eat soil in Geita District are exposed to potentially high levels of chemical elements, depending upon frequency of consumption, daily amount consumed and the source location of soil eaten

TMEM120A and B: Nuclear Envelope Transmembrane Proteins Important for Adipocyte Differentiation

<div><p>Recent work indicates that the nuclear envelope is a major signaling node for the cell that can influence tissue differentiation processes. Here we present two nuclear envelope trans-membrane proteins TMEM120A and TMEM120B that are paralogs encoded by the <i>Tmem120A</i> and <i>Tmem120B</i> genes. The TMEM120 proteins are expressed preferentially in fat and both are induced during 3T3-L1 adipocyte differentiation. Knockdown of one or the other protein altered expression of several genes required for adipocyte differentiation, <i>Gata3</i>, <i>Fasn</i>, <i>Glut4</i>, while knockdown of both together additionally affected <i>Pparg</i> and <i>Adipoq</i>. The double knockdown also increased the strength of effects, reducing for example <i>Glut4</i> levels by 95% compared to control 3T3-L1 cells upon pharmacologically induced differentiation. Accordingly, TMEM120A and B knockdown individually and together impacted on adipocyte differentiation/metabolism as measured by lipid accumulation through binding of Oil Red O and coherent anti-Stokes Raman scattering microscopy (CARS). The nuclear envelope is linked to several lipodystrophies through mutations in lamin A; however, lamin A is widely expressed. Thus it is possible that the TMEM120A and B fat-specific nuclear envelope transmembrane proteins may play a contributory role in the tissue-specific pathology of this disorder or in the wider problem of obesity.</p></div

From lamins to lamina: a structural perspective

Lamin proteins are the major constituents of the nuclear lamina, a proteinaceous network that lines the inner nuclear membrane. Primarily, the nuclear lamina provides structural support for the nucleus and the nuclear envelope; however, lamins and their associated proteins are also involved in most of the nuclear processes, including DNA replication and repair, regulation of gene expression, and signaling. Mutations in human lamin A and associated proteins were found to cause a large number of diseases, termed 'laminopathies.' These diseases include muscular dystrophies, lipodystrophies, neuropathies, and premature aging syndromes. Despite the growing number of studies on lamins and their associated proteins, the molecular organization of lamins in health and disease is still elusive. Likewise, there is no comprehensive view how mutations in lamins result in a plethora of diseases, selectively affecting different tissues. Here, we discuss some of the structural aspects of lamins and the nuclear lamina organization, in light of recent results

CLINICAL NUTRITION

Background & aims: We conducted a multicentre study to assess nutritional risk at hospital admission, hospital-associated iatrogenic malnutrition and the status of nutritional support in Turkish hospitals. Methods: A database which allowed for online submission of hospital and patient data was developed. A nutritional risk screening system (NRS-2002) was applied to all patients and repeated weekly in patients with hospital stays greater than one week and no invasive procedures. Patient-specific nutritional support was recorded during the study period. Results: Thirty-four hospitals from 19 cities contributed data from 29,139 patients. On admission, 15% of patients had nutritional risk. Nutritional risk was common (52%) in intensive care unit patients and lowest (3.9%) in otorhinolaryngology patients. Only 51.8% of patients with nutritional risk received nutritional support. Nutritional risk was present in 6.25% of patients at the end of the first week and 5.2% at the end of the second week, independent of nutritional support. In patients with nutritional risk on admission who were hospitalized for two weeks and received nutritional support, the NRS-2002 score remained >= 3 in 83% of cases. Conclusions: Nutritional risk is common in hospitalized Turkish patients. While patients at nutritional risk often do not receive nutritional support when hospitalized, nutritional risk occurs independent of nutritional support. (C) 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved

A Flow Cytometry-Based Screen of Nuclear Envelope Transmembrane Proteins Identifies NET4/Tmem53 as Involved in Stress-Dependent Cell Cycle Withdrawal

Disruption of cell cycle regulation is one mechanism proposed for how nuclear envelope protein mutation can cause disease. Thus far only a few nuclear envelope proteins have been tested/found to affect cell cycle progression: to identify others, 39 novel nuclear envelope transmembrane proteins were screened for their ability to alter flow cytometry cell cycle/DNA content profiles when exogenously expressed. Eight had notable effects with seven increasing and one decreasing the 4N∶2N ratio. We subsequently focused on NET4/Tmem53 that lost its effects in p53−/− cells and retinoblastoma protein-deficient cells. NET4/TMEM53 knockdown by siRNA altered flow cytometry cell cycle/DNA content profiles in a similar way as overexpression. NET4/TMEM53 knockdown did not affect total retinoblastoma protein levels, unlike nuclear envelope-associated proteins Lamin A and LAP2α. However, a decrease in phosphorylated retinoblastoma protein was observed along with a doubling of p53 levels and a 7-fold increase in p21. Consequently cells withdrew from the cell cycle, which was confirmed in MRC5 cells by a drop in the percentage of cells expressing Ki-67 antigen and an increase in the number of cells stained for ß-galactosidase. The ß-galactosidase upregulation suggests that cells become prematurely senescent. Finally, the changes in retinoblastoma protein, p53, and p21 resulting from loss of NET4/Tmem53 were dependent upon active p38 MAP kinase. The finding that roughly a fifth of nuclear envelope transmembrane proteins screened yielded alterations in flow cytometry cell cycle/DNA content profiles suggests a much greater influence of the nuclear envelope on the cell cycle than is widely held