bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Genome-Wide RNAi Screen for Enhancers of par Mutants Reveals New Contributors to Early Embryonic Polarity in Caenorhabditis elegans
Authors: Morton Diane G , Hoose Wendy A , Kemphues Kenneth J 
Published: August 2012

Abstract
The par genes of Caenorhabditis elegans are essential for establishment and maintenance of early embryo polarity and their homologs in other organisms are crucial polarity regulators in diverse cell types. Forward genetic screens and simple RNAi depletion screens have identified additional conserved regulators of polarity in C. elegans; genes with redundant functions, however, will be missed by these approaches. To identify such genes, we have performed a genome-wide RNAi screen for enhancers of lethality in conditional par-1 and par-4 mutants. We have identified 18 genes for which depletion is synthetically lethal with par-1 or par-4, or both, but produces little embryo lethality in wild type. Fifteen of the 18 genes identified in our screen are not previously known to function in C. elegans embryo polarity and 11 of them also increase lethality in a par-2 mutant. Among the strongest synthetic lethal genes, polarity defects are more apparent in par-2 early embryos than in par-1 or par-4, except for strd-1(RNAi), which enhances early polarity phenotypes in all three mutants. One strong enhancer of par-1 and par-2 lethality, F25B5.2, corresponds to nop-1, a regulator of actomyosin contractility for which the molecular identity was previously unknown. Other putative polarity enhancers identified in our screen encode cytoskeletal and membrane proteins, kinases, chaperones, and sumoylation and deubiquitylation proteins. Further studies of these genes should give mechanistic insight into pathways regulating establishment and maintenance of cell polarity.
Nonrandom X Chromosome Inactivation Is Influenced by Multiple Regions on the Murine X Chromosome
Authors: Thorvaldsen Joanne L , Krapp Christopher , Willard Huntington F , Bartolomei Marisa S 
Published: August 2012

AbstractDuring the development of female mammals, one of the two X chromosomes is inactivated, serving as a dosage-compensation mechanism to equalize the expression of X-linked genes in females and males. While the choice of which X chromosome to inactivate is normally random, X chromosome inactivation can be skewed in F1 hybrid mice, as determined by alleles at the X chromosome controlling element (Xce), a locus defined genetically by Cattanach over 40 years ago. Four Xce alleles have been defined in inbred mice in order of the tendency of the X chromosome to remain active: Xcea &lt; Xceb &lt; Xcec &lt; Xced. While the identity of the Xce locus remains unknown, previous efforts to map sequences responsible for the Xce effect in hybrid mice have localized the Xce to candidate regions that overlap the X chromosome inactivation center (Xic), which includes the Xist and Tsix genes. Here, we have intercrossed 129S1/SvImJ, which carries the Xcea allele, and Mus musculus castaneus EiJ, which carries the Xcec allele, to generate recombinant lines with single or double recombinant breakpoints near or within the Xce candidate region. In female progeny of 129S1/SvImJ females mated to recombinant males, we have measured the X chromosome inactivation ratio using allele-specific expression assays of genes on the X chromosome. We have identified regions, both proximal and distal to Xist/Tsix, that contribute to the choice of which X chromosome to inactivate, indicating that multiple elements on the X chromosome contribute to the Xce.
Dermatoglyphic Evaluation in Subjects and Parents of Cleft Lip with and without Cleft Palate
Authors: Saxena Runjhun Subhanand , David Maria Priscilla , Indira A.P. 
Published: August 2012

Objectives Dermatoglyphic patterns make good material for genetic studies because they remain stable throughout life. Given that the primary palate, lip, and dermal ridges develop during the same period of intrauterine life, the genetic message contained in the genome can be deciphered during this period and is reflected by dermatoglyphics. This study was undertaken to compare the dermatoglyphic patterns in subjects with clefts and controls and both their parents to study the genetic etiology. Methods A total of 294 subjects (48 cleft subjects and 50 healthy controls with both their parents) were selected. Finger and palm prints of all were recorded using the ink method. Results Increased frequency of loops and arches and low mean total ridge count was observed in cleft subjects. Increased frequency of loops and arches with decreased frequency of whorls, mean total ridge count, and atd angle of right hand was found in parents of cleft group as compared with the parents of the controls. Conclusion Dermatoglyphic patterns have considerable variances. They can be used to study genetic etiology and as an educational tool for genetic counseling.
Three-Dimensional Reconstruction of Large Secondary Alveolar Cleft by Two-Stage Distraction
Authors: Rachmiel Adi , Emodi Omri , Aizenbud Dror 
Published: August 2012

Objective Our aim is to demonstrate a method for reconstruction of a wide alveolar cleft before implant placement. Patient and Method An adult patient with a unilateral cleft palate and a wide alveolar and maxillary bone defect underwent transport distraction osteogenesis to medialize the left segment and reduce the alveolar cleft to a minimum. Removal of the transport distraction device was accompanied by autogenous bone grafting to the remaining alveolar defect in the medial cleft, attaining an osseous closure with adequate soft-tissue coverage. Three months later, vertical alveolar distraction of the newly reconstructed bone was performed. Implants were placed after the removal of the distraction device. Results Alveolar bone was transported forward 20 mm followed by 15 mm vertical distraction. The large cleft palate defect was reconstructed in three dimensions by the two-stage distraction osteogenesis, and the soft tissues were expanded to achieve functional correction. After removal of the distraction device, dental implants were osteointegrated in the newly reconstructed bone for fixed dental rehabilitation. Conclusions The two-stage distraction allowed gradual closure of a large defect three dimensionally. This method can be safely performed not only in patients undergoing initial treatment for large alveolar clefts but also after failed bone grafting.
Diuron Occurrence and Distribution in Soil and Surface and Ground Water Associated with Grass Seed Production
Authors: Field Jennifer A. , Reed Ralph L. , Sawyer Thomas E. , Griffith Steven M. , Wigington P. J. 
Published: August 2012

ABSTRACTLittle is known about the occurrence and distribution of the herbicide diuron [3‐(3,4‐dichlorophenyl)‐1,1‐dimethyl urea] in soil, ground water, and surface water in areas affected by grass‐seed production. A field study was designed to investigate the occurrence and distribution of diuron and its transformation products at a poorly drained field site located along an intermittent tributary of Lake Creek in the southern Willamette Valley of Oregon. The experimental sites consisted of a field under commercial grass seed production with a cultivated riparian zone and a second site that was part of the same grass seed field but with a noncultivated riparian zone. Diuron and its transformation product DCPMU [3‐(3,4‐dichlorophenyl)‐1‐methylurea] were the only significant residues detected in this study. Concentrations of diuron in surface water declined from a maximum of 28 μg/L immediately following application to low levels that persisted as long as flow was present. Diuron and DCPMU concentrations in shallow ground water (15–36 cm below ground surface) were highest (2–13 μg/L) in the zone immediately adjacent (0.5 m) to Lake Creek and indicated the influence of stream water on shallow ground water near the stream. Diuron and DCPMU detected in soil prior to the second season's application indicated the persistence of diuron and DCPMU from the previous year's application. Surface runoff during the rainy season removes only a very small percentage (<1%) of the applied herbicide. In addition, no evidence was obtained for the downward transport of diuron or its transformation products to deep ground water.
Obstetric Nephrology
Authors: Odutayo Ayodele , Hladunewich Michelle 
Published: August 2012

Summary
Glomerular hyperfiltration, altered tubular function, and shifts in electrolyte-fluid balance are among the hallmark renal physiologic changes that characterize a healthy pregnancy. These adjustments are not only critical to maternal and fetal well being, but also provide the clinical context for identifying gestational aberrations in renal function and electrolyte composition. Systemic vasodilation characterizes early gestation and produces increments in renal plasma flow and GFR, the latter of which is maintained into the postpartum period. In addition, renal tubular changes allow for the accumulation of nutrients and electrolytes necessary for fetal growth such that wasting of proteins, glucose, and amino acids in urine is limited in pregnancy and total body stores of electrolytes increase throughout gestation. Substantial insight into the mechanisms underlying these complex adjustments can be gleaned from the available animal and human literature, but our understanding in many areas remains incomplete. This article reviews the available literature on renal adaptation to normal pregnancy, including renal function, tubular function, and electrolyte-fluid balance, along with the clinical ramifications of these adjustments, the limitations of the existing literature, and suggestions for future studies.
CKD, Plasma Lipids, and Common Carotid Intima-Media Thickness
Authors: Lamprea-Montealegre Julio A. , Astor Brad C. , McClelland Robin L. , de Boer Ian H. , Burke Gregory L. , Sibley Christopher T. , O’Leary Daniel , Sharrett A. Richey , Szklo Moyses 
Published: August 2012

Summary

Background and objectives
Altered levels of atherogenic lipoproteins have been shown to be common in mild kidney dysfunction. This study sought to determine the associations between plasma lipids (including LDL particle distribution) and subclinical atherosclerosis measured by the common carotid intima-media thickness (IMT) across levels of estimated GFR (eGFR) and to assess whether inflammation modifies these associations.

Design, setting, participants, & measurements
Cross-sectional analyses of 6572 participants in the Multi-Ethnic Study of Atherosclerosis enrolled from 2000 to 2002 were performed.

Results
CKD, defined as eGFR <60 ml/min per 1.73 m2, was present in 853 individuals (13.0%). Associations of total cholesterol and LDL cholesterol (LDL-C) with IMT were J shaped, particularly among participants with CKD (P value for interaction, P=0.01). HDL cholesterol (HDL-C) and small-dense LDL-C were consistently and linearly associated with IMT across levels of eGFR. The results showed differences in IMT of −21.41 (95% confidence interval, −41.00, −1.57) in eGFR ≥60 and −58.49 (−126.61, 9.63) in eGFR <60 per unit difference in log-transformed HDL-C, and 4.83 (3.16, 6.50) in eGFR ≥60 and 7.48 (1.45, 13.50) in eGFR <60 per 100 nmol/L difference in small-dense LDL. Among participants with CKD, inflammation significantly modified the associations of total cholesterol and LDL-C with IMT (P values for interaction, P<0.01 and P<0.001, respectively).

Conclusions
Compared with total cholesterol and LDL-C, abnormalities in HDL-C and small-dense LDL-C are more strongly and consistently associated with subclinical atherosclerosis in CKD. Inflammation modifies the association between total cholesterol and LDL-C with IMT.
Onco-Nephrology
Authors: Rosner Mitchell H. , Dalkin Alan C. 
Published: August 2012

Summary
Hypercalcemia complicates the course of 10%–30% of all patients with malignancies and can be a sign of very poor prognosis and advanced malignancy. Prompt recognition of the nonspecific signs and symptoms of hypercalcemia and institution of therapy can be lifesaving, affording the opportunity to address the underlying etiology. The mechanisms of malignancy-associated hypercalcemia generally fall into three categories: humoral hypercalcemia due to secreted factors (such as parathyroid-related hormone), local osteolysis due to tumor invasion of bone, and absorptive hypercalcemia due to excess vitamin D produced by malignancies. The mainstays of therapy for hypercalcemia are aggressive intravenous volume expansion with saline, bisphosphonate therapy, and perhaps loop diuretics. Adjunctive therapy may include calcitonin and corticosteroids. In refractory cases, gallium nitrate and perhaps denosumab are alternatives. In patients presenting with severe AKI, hemodialysis with a low-calcium bath can be effective. In most cases, therapy normalizes calcium levels and allows for palliation or curative therapy of the malignancy.
Onco-Nephrology
Authors: Perazella Mark A. 
Published: August 2012

Summary
Despite dramatic improvements in patient survival and drug tolerability, nephrotoxicity remains an important complication of chemotherapy. Adverse renal effects occur because of innate drug toxicity and a number of patient- and drug-related factors. To provide cutting edge care for these patients, nephrologists and oncologists must be familiar with the nephrotoxicity of these drugs, particularly their associated clinical and laboratory manifestations. Rapid diagnosis, targeted treatment, and supportive care are critical to improving care for these patients. Unfortunately, some patients who develop nephrotoxicity will be left with long-term complications such as chronic tubulopathies and CKD. Onco-Nephrology is a new area that is rapidly expanding and requires a close working relationship between oncologists and nephrologists.
Onco-Nephrology
Authors: Lam Albert Q. , Humphreys Benjamin D. 
Published: August 2012

Summary
AKI is common in patients with cancer, and it causes interruptions in therapy and increased hospital length of stay, cost, and mortality. Although cancer patients are susceptible to all of the usual causes of AKI in patients without cancer, there are a number of AKI syndromes that occur more frequently or are unique to this patient population. AKI also confers substantially increased risk of short-term death, and the ability to reverse AKI portends a better outcome in some cancers, such as multiple myeloma. Several trends in oncology, including increased survival, better supportive care, older patients who have received multiple chemotherapy regimens, and new therapeutic options, are driving an increase in the numbers of cancer patients who develop AKI. As a result, nephrologists should be increasingly familiar with the diagnosis, management, and treatment of AKI in this setting. Here, we summarize recent data on epidemiology of AKI in cancer patients, describe the most common AKI syndromes in this population, and highlight emerging areas in the growing field of onconephrology.
Onco-Nephrology
Authors: Wilson F. Perry , Berns Jeffrey S. 
Published: August 2012

SummaryTumor lysis syndrome (TLS) describes the clinical and laboratory sequelae that result from the rapid release of intracellular contents of dying cancer cells. It is characterized by the release of potassium, phosphorous, and nucleic acids from cancer cells into the blood stream, with the potential to cause hyperkalemia; hyperphosphatemia and secondary hypocalcemia; hyperuricemia; AKI; and, should usual homeostatic mechanisms fail, death. TLS most commonly follows treatment of hematologic malignancies, such as acute lymphocytic or lymphoblastic leukemia, acute myeloid leukemia, and Burkitt lymphoma, but also occurs after treatment of other bulky or rapidly growing tumors, particularly if the patient is highly sensitive to the effects of cytotoxic chemotherapy. Prevention and treatment depend on prompt recognition of patients at risk, volume repletion, allopurinol, rasburicase (a novel recombinant urate oxidase), and, when indicated, dialysis.
Lupus Nephritis
Authors: Rovin Brad H. , Parikh Samir V. , Hebert Lee A. , Chan Tak Mao , Mok Chi Chiu , Ginzler Ellen M. , Hooi Lai Seong , Brunetta Paul , Maciuca Romeo , Solomons Neil 
Published: August 2012

Summary
Severe lupus nephritis is an aggressive disease that requires an aggressive approach to treatment. Recent randomized clinical trials showed that mycophenolate mofetil compared favorably with cyclophosphamide (traditional approach) for remission induction. Consequently, mycophenolate mofetil is now commonly recommended as first-line therapy. Nevertheless, the role of mycophenolate mofetil in treating severe lupus nephritis is unclear, because such patients were excluded from these trials. With this limitation as background, this work addresses the question of mycophenolate mofetil for induction therapy for severe lupus nephritis. We performed a systematic review of the outcomes of treating severe lupus nephritis with mycophenolate mofetil or cyclophosphamide. Because no studies directly addressed this question, these data were extracted from the published literature or obtained by personal communications from investigators. There is no universally accepted definition, and therefore, severe lupus nephritis was arbitrarily defined by renal histology, resistance to therapy, or level of kidney function at presentation. For each trial analyzed, we determined the partial and complete remission rates. Long-term outcomes were compared when available. The pooled results suggest that mycophenolate mofetil and cyclophosphamide are equally effective in inducing remission of severe lupus nephritis. However, relapse rates and risk of developing ESRD were higher for mycophenolate mofetil compared with cyclophosphamide. In conclusion, in the short term, mycophenolate mofetil and cyclophosphamide are about equal in inducing remission. However, long-term outcomes suggest better preservation of kidney function and fewer relapses with cyclophosphamide therapy. Therefore, mycophenolate mofetil should not yet be considered the induction drug of choice for severe lupus nephritis.
Obstetric Nephrology
Authors: Stanhope Todd J. , White Wendy M. , Moder Kevin G. , Smyth Andrew , Garovic Vesna D. 
Published: August 2012

Summary
SLE is a multi-organ autoimmune disease that affects women of childbearing age. Renal involvement in the form of either active lupus nephritis (LN) at the time of conception, or a LN new onset or flare during pregnancy increases the risks of preterm delivery, pre-eclampsia, maternal mortality, fetal/neonatal demise, and intrauterine growth restriction. Consequently, current recommendations advise that the affected woman achieve a stable remission of her renal disease for at least 6 months before conception. Hormonal and immune system changes in pregnancy may affect disease activity and progression, and published evidence suggests that there is an increased risk for a LN flare during pregnancy. The major goal of immunosuppressive therapy in pregnancy is control of disease activity with medications that are relatively safe for a growing fetus. Therefore, the use of mycophenolate mofetil, due to increasing evidence supporting its teratogenicity, is contraindicated during pregnancy. Worsening proteinuria, which commonly occurs in proteinuric renal diseases toward the end of pregnancy, should be differentiated from a LN flare and/or pre-eclampsia, a pregnancy-specific condition clinically characterized by hypertension and proteinuria. These considerations present challenges that underscore the importance of a multidisciplinary team approach when caring for these patients, including a nephrologist, rheumatologist, and obstetrician who have experience with these pregnancy-related complications. This review discusses the pathogenesis, maternal and fetal risks, and management pertinent to SLE patients with new onset or a history of LN predating pregnancy.
Obstetric Nephrology
Authors: Fakhouri Fadi , Vercel Caroline , Frémeaux-Bacchi Véronique 
Published: August 2012

Summary
AKI in pregnancy remains a cause of significant fetomaternal mortality and morbidity, particularly in developing countries. Hypertensive complications of pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low platelets count syndrome) are the leading cause of AKI in pregnancy worldwide. Thrombotic microangiopathy is another peculiar and devastating cause of AKI in pregnancy. During the last decade, our understanding, and in some cases, our management, of these causes of AKI in pregnancy has dramatically improved. For instance, convincing data have linked pre-eclampsia/eclampsia to an increase in circulating antiangiogenic factors soluble Flt 1 and endoglin, which induce endothelial cell dysfunction, hypertension, and proteinuria. Several distinct pathogenic mechanisms underlying thrombotic microangiopathy, including thrombotic microangiopathy occurring during pregnancy, have been established. Thrombotic microangiopathy, which can present as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, can be reclassified in four potentially overlapping subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency-related thrombotic microangiopathy, complement alternative pathway dysregulation-related thrombotic microangiopathy, secondary thrombotic microangiopathy (verotoxin and antiangiogenic drugs), and thrombotic microangiopathy of undetermined mechanism. In most cases, pregnancy is only a precipitating factor for thrombotic microangiopathy. Treatment of thrombotic microangiopathy occurring during pregnancy should be tailored to the underlying pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 serum activity in the setting of thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B cell-depleting therapy and (2) inhibition of complement alternative pathway activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody (eculizumab).
Dental microwear texture analysis of late Pliocene Procynocephalus subhimalayanus (Primates: Cercopithecidae) of the Upper Siwaliks, India
Authors: Williams Frank , Holmes Noelle 
Published: August 2012

Abstract
Late Pliocene Procynocephalus subhimalayanus from the Upper Siwaliks, India is known from only three specimens. The dietary proclivities of this taxon have implications for reconstructing the paleoecology of the Upper Siwaliks. The dental microwear texture properties of Procynocephalus are compared to those from extant tropical forest primates including Alouatta palliata (n = 11), Cebus apella (n = 13), Gorilla gorilla (n = 9), Lophocebus albigena (n = 15) and Trachypithecus cristatus (n = 12). Dental microwear textures are generated by scanning the surface enamel of Facet 9 using white-light confocal microscopy at 100x. Four variables were extracted from scale-sensitive fractal analysis, and the data were ranked before ANOVA with post-hoc tests of significance and multivariate analyses were performed. Procynocephalus clusters closest to Lophocebus, Cebus and some Gorilla specimens suggesting hard-object feeding characterized a portion of its diet. The dental microwear texture of Procynocephalus supports interpretations of widespread grasslands of the Late Pliocene Kansal Formation (Pinjor zone). The extreme enamel complexity characterizing Procynocephalus may derive from consumption of underground storage organs, or other foods with high grit loads. Foods consumed near ground level carry a heavy load of abrasive minerals possibly contributing to greater enamel surface complexity and textural fill volume.