bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reauthorization of PDUFA: An Exercise in Post-Market Drug Safety Reform
Authors: Chang Peter 
Published: January 2021

The recent withdrawals of Vioxx, Celebrex, and other drugs from the market have spurred high-profile hearings in Congress and increased concern over the state of drug regulation in consumer protection and academic circles. This renewed focus on national drug safety has translated ineluctably into new legislation designed to mitigate that outcry. The most notable example, the passage of the Food and Drug Administration Amendments Act (FDAAA) this past September, is at least partly intended as a response to an apparent lack of public confidence in existing drug safety practices.Of the many provisions in the FDAAA, perhaps none carries greater implications for drug safety than the reauthorized Prescription Drug User Fee Act (PDUFA). Now in its fourth iteration, the newest PDUFA differs in important respects from the statute it supersedes.
Malpractice & Negligence: Cal. Supreme Court Clarifies Negligence Provisions under State’s Elder Abuse Act
Authors: Carlson Kendra 
Published: January 2021

The Supreme Court of California held, in Delaney v. Baker, 82 Cal. Rptr. 2d 610 (1999), that the heightened remedies available under the Elder Abuse Act (Act), Cal. Welf. & Inst. Code, §§ 15657,15657.2 (West 1998), apply to health care providers who engage in reckless neglect of an elder adult. The court interpreted two sections of the Act: (1) section 15657, which provides for enhanced remedies for reckless neglect; and (2) section 15657.2, which limits recovery for actions based on “professional negligence.” The court held that reckless neglect is distinct from professional negligence and therefore the restrictions on remedies against health care providers for professional negligence are inapplicable.Kay Delaney sued Meadowood, a skilled nursing facility (SNF), after a resident, her mother, died. Evidence at trial indicated that Rose Wallien, the decedent, was left lying in her own urine and feces for extended periods of time and had stage I11 and IV pressure sores on her ankles, feet, and buttocks at the time of her death.
Posterior Endoscope-Assisted Diskectomy Is an Effective Technique for Cervical Soft Disk Herniation
Authors: Karaoglu Derya Gündoğdu , Polat Omer , Uckun Ozhan Merzuk , Karadeniz Resul , Belen Deniz , Dalgic Ali 
Published: January 2021

Abstract
Objective To evaluate the clinicoradiologic conditions of patients with a herniated cervical disk who were treated with percutaneous endoscope-assisted cervical diskectomy.
Materials and Methods The medical data of 27 patients (16 men and 11 women; mean age: 40.9 years) who were operated on with the posterior endoscope-assisted cervical diskectomy method were reviewed retrospectively. The mean follow-up was 35.1 months, and the patients were assessed with combined preoperative and postoperative visual analog scale (VAS), Prolo Functional Economic Outcome Rating scale, MacNab scale, and clinical imaging.
Results The mean preoperative VAS level was 8.6 (range: 7–10), and mean Prolo score was 2.5 (range: 2–5). A postoperative assessment performed 1 week postsurgery found a mean VAS level of 2.1 (range: 0–4). At the final examination, the mean VAS level was 0.81 (range: 0–3), and the mean Prolo score was 4.5 (range: 3–5). The final MacNab scale scores were 62.9%, excellent; 25.9%, good; 7.4%, moderate; and 3.7%, poor.
Conclusion Percutaneous endoscope-assisted cervical diskectomy is a suitable and effective treatment method for soft cervical disk herniation.
Prognostic effects of arterial carbon dioxide levels in patients hospitalized into the cardiac intensive care unit for acute heart failure
Authors: Kato Takao , Kasai Takatoshi , Suda Shoko , Sato Akihiro , Ishiwata Sayaki , Yatsu Shoichiro , Matsumoto Hiroki , Shitara Jun , Shimizu Megumi , Murata Azusa , Kagiyama Nobuyuki , Hiki Masaru , Matsue Yuya , Naito Ryo , Takagi Atsutoshi , Daida Hiroyuki 
Published: January 2021

Abstract

Aims
Although both hypercapnia and hypocapnia are common in acute heart failure (AHF) patients, routine assessment of arterial blood gas is not recommended. Additionally, no association between hypercapnia and increased mortality has been found, and the prognostic value of hypocapnia in AHF patients remains to be elucidated. In this observational study, we aimed to investigate the relationship between partial pressure of arterial carbon dioxide (PaCO2), especially low PaCO2, and long-term mortality in AHF patients.

Methods and results
Acute heart failure patients hospitalized in the cardiac intensive care unit of our institution between 2007 and 2011 were screened. All eligible patients were divided into two groups based on the inflection point (i.e. 31.0 mmHg) of the 3-knot cubic spline curve of the hazard ratio (HR), with a PaCO2 of 40 mmHg as a reference. The association between PaCO2 levels and all-cause mortality was assessed using Cox proportional hazards regression models. Among 435 patients with a median follow-up of 1.8 years, 115 (26.4%) died. Adjusted analysis with relevant variables as confounders indicated that PaCO2 &lt;31 mmHg was significantly associated with increased all-cause mortality [HR 1.71, 95% confidence interval (CI) 1.05–2.79; P = 0.032]. When PaCO2 was considered as a continuous variable, the lower was the log-transformed PaCO2, the greater was the increased risk of mortality (HR 0.71, 95% CI 0.52–0.96; P = 0.024).

Conclusions
In AHF patients, lower PaCO2 at admission was associated with increased long-term mortality risk.
CYTOPLASMIC INHERITANCE OF A CELL SURFACE ANTIGEN IN THE MOUSE
Authors: Lindahl Kirsten Fischer , Hausmann Barbara 
Published: January 2021

ABSTRACT
Mta is a cell surface antigen of the mouse and serves as a target for specific T killer lymphocytes. Using a killer cell assay, the antigen has been found in 72 strains of laboratory mice and, with one exception, in all tested samples of mice caught in the wild or bred from such, including Mus molossinus, Mus castaneus and Mus spretus. Five strains of rats, non-inbred NMRI mice, most substrains of NZB mice and the closely related strain NZO are negative for Mta. In reciprocal F1 crosses between several Mta+ and two Mta- strains, the antigen is maternally transmitted; that is, Mta+ females bear only positive offspring, whereas Mta- females bear only negative offspring, regardless of the genotype of the male. Since 34 foster-nursed mice had the Mta type of their genetic mothers, the factor that determines expression of Mta must be transmitted before birth and not via the milk. The cytoplasmic genes of Mta+ strains have been combined with the chromosomal genes of Mta- strains, and vice versa, by repeated backcrossing. All progeny retained the Mta type of their maternal lines. Thus, the Mta type is determined solely by maternal inheritance and is not influenced by chromosomal genes. We found no evidence of incompatibility between the cytoplasmic factors and nuclear genes of Mta- and Mta+ strains.
THE PLEIOTROPIC ts15 MUTATION OF E. COLI IS AN IS1 INSERTION IN THE rho STRUCTURAL GENE
Authors: Gulletta Elio , Das Asis , Adhya Sankar 
Published: January 2021

ABSTRACT
Rho protein regulates transcription termination in E. coli. Some of the temperature-sensitive mutants defective in Rho protein, e.g., ts15, show remarkable pleiotropic phenotypes. The ts mutations map between the ilv and cya loci on the E. coli chromosome. We have cloned the gene that restores the wild-type phenotypes of these mutants. Genetic and biochemical characterizations have shown that the cloned DNA segment carries the structural gene for the Rho polypeptide. Analysis of the rhots15 mutation has revealed the presence of an IS1 insertion in the carboxy terminal segment of the rho cistron, thereby truncating the 52-kilodalton (kd) Rho polypeptide to a 50-kd size and also making it thermolabile. This provides an example of how an IS1 insertion mutation can cause a TS phenotype. We have also shown that the multiple phenotypes of the mutant cell, including the temperature sensitivity, are caused by a single mutation (rhots15::IS1) in the rho structural gene. How a rho structural gene mutation may cause such pleiotropy is discussed.
GENETIC ANALYSIS OF B2t, THE STRUCTURAL GENE FOR A TESTIS-SPECIFIC β-TUBULIN SUBUNIT IN DROSOPHILA MELANOGASTER
Authors: Kemphues Kenneth J , Raff Elizabeth C , Kaufman Thomas C 
Published: January 2021

ABSTRACT
Genetic analysis of the B2t locus has resulted in the recovery of four recessive mutations in the B2t structural gene and a deficiency that deletes the locus. Two of the mutations were recovered as suppressors of B2tD, a dominant male sterile mutation at the locus, and two were induced on wild-type chromosomes. All four mutant genes encode β2-tubulin subunits that are synthesized at normal rates but do not accumulate. All mutants are completely male sterile as homozygotes.
THE CHARACTERIZATION OF α-GLYCEROPHOSPHATE DEHYDROGENASE MUTANTS IN DROSOPHILA MELANOGASTER
Authors: Kotarski Michael A , Pickert Sally , Leonard Deborah A , LaRosa Gregory J , MacIntyre Ross J 
Published: January 2021

ABSTRACT
Thirty mutants of α-glycerophosphate dehydrogenase (αGPDH, EC 1.1.1.8) from Drosophila melanogaster were produced with the chemical mutagen ethyl methanesulfonate (EMS). These mutants and nine others previously obtained have been characterized with respect to level of enzymatic activity, viability, flight ability, and presence of cross-reacting material (CRM). The presence of αGPDH mRNA in several of the mutants has been tested by in vitro translation. There are strong correlations between the level of enzyme activity, viability and flight ability. Thirteen of the mutants are CRM- by solution immunoprecipitation experiments, but of these, only three are CRM- by a more sensitive 125I-protein A-based radioimmune gel assay. The viability of the three CRM- mutants suggests that the absence of αGPDH protein is not a lethal condition. The immunoprecipitated protein of the low activity mutant, αGpdhnGL3, has a smaller apparent molecular weight on polyacrylamide-SDS gels than does the protein from wild type. Criteria for the identification of nonsense mutations in Drosophila are discussed.
GENETIC VARIATION AFFECTING THE EXPRESSION OF CATALASE IN DROSOPHILA MELANOGASTER: CORRELATIONS WITH RATES OF ENZYME SYNTHESIS AND DEGRADATION
Authors: Bewley Glenn C , Laurie-Ahlberg Cathy C 
Published: January 2021

ABSTRACT
Both second and third chromosome substitution lines isolated from natural populations of Drosophila melanogaster affect the expression of catalase (EC 1.11.1.6) at both the larval and adult stages of development. In each case, the level of catalase activity is strongly related to the level of catalase-specific cross-reacting material. Turnover studies employing the catalase inhibitor 3-amino-1,2,4-triazole were conducted on a selected number of lines. Although the variation in steady state levels of catalase protein was highly significant among lines, variation in intracellular degradation rate was not. These results suggest that the different steady state levels observed among lines largely reflect different rates of catalase synthesis.
GENETIC ANALYSIS OF BROWN ADIPOSE TISSUE, OBESITY AND GROWTH IN MICE
Authors: Saxton A M , Eisen E J 
Published: January 2021

ABSTRACT
The hypothesis developed from single-gene mutant obese rodents that brown adipose tissue (BAT), through its thermogenic ability, is an important factor in the development of obesity, was tested in a randombred population of mice in which degree of adiposity is polygenically determined. Additive direct genetic parameters for measures of body size, lean, fatness and BAT at 6 wk of age were estimated under control and high-fat postweaning dietary regimens. Heritabilities were generally similar for the two diets. However, the lipid-free dry (LFD) component of BAT had a heritability estimate of 0.70 ± 0.26 on the control diet, but only 0.09 ± 0.20 on the high-fat diet. For all traits, genotype by diet interactions indicated that additive direct genetic rankings were not significantly different for the two diets. Based on estimates of genetic parameters in the control diet, selection for 6-wk body weight or 3- to 6-wk gain is expected to increase body size and adiposity. Selection for BAT weight is predicted to result in large, lean individuals. However, selection for the LFD content of BAT, generally believed to be a better indicator of thermogenic ability, is predicted to increase fatness as well as body size. Selection for LFD as a proportion of 6-wk body weight reduced the expected correlated response in fatness. It was concluded that BAT does not play a major role in determining the correlated response in obesity that is often found in populations selected for large body size.
PHOSPHOGLUCOSE ISOMERASE EXPRESSION IN SPECIES OF CLARKIA WITH AND WITHOUT A DUPLICATION OF THE CODING GENE
Authors: Gottlieb L D , Higgins R C 
Published: January 2021

ABSTRACT
The duplication of the nuclear gene specifying the cytosolic isozyme of phosphoglucose isomerase (PGI; EC 5.3.1.9) arose within Clarkia, a genus of annual plants native to California, and now characterizes about half of the diploid species of this genus. Evidence obtained by immunological inhibition and titration of crude leaf extracts demonstrated that species with and without the duplication have the same levels of cytosolic to total PGI (the sum of the cytosolic and plastid PGI activities). The immunological studies were carried out with a specific anticytosolic PGI antiserum and were fully supported by a densitometric analysis of the electrophoretically separated isozymes. Densitometric examination of electrophoretically separated PGIs in 11 vegetable species revealed only two levels of cytosolic to total PGI activities, one of which was the same as in Clarkia. This suggests that only certain levels of the cytosolic isozyme are compatible with proper operation of the cytosolic PGI reaction and make it likely that some form of genic or metabolic regulation has evolved that compensates for the PGI duplication.
CHARACTERIZATION OF ALLOZYME NULL AND LOW ACTIVITY ALLELES FROM TWO NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER
Authors: Burkhart Barbara Dickson , Montgomery Elizabeth , Langley Charles H , Voelker Robert A 
Published: January 2021

ABSTRACT
Null and low enzyme activity alleles recovered from two natural populations were analyzed for a number of genetic and biochemical properties. Analysis of 58 mutations at 14 loci showed that all but one allele were genetically viable and fertile, four alleles were associated with chromosome rearrangements, 28 alleles retained some enzyme activity, 13 alleles formed an active heterodimer with active alleles and five alleles showed partial interallelic complementation. Available evidence indicates that this sample includes mutations resulting from lesions in both coding and regulatory sequences. Certain mutations may be caused by transposable element insertions.
PLEIOTROPIC OVERDOMINANCE AND THE MAINTENANCE OF GENETIC VARIATION IN POLYGENIC CHARACTERS
Authors: Gillespie John H 
Published: January 2021

ABSTRACT
A model of selection is described in which optimizing phenotypic selection is combined with pleiotropic overdominance. Thus, the role that mutation commonly plays in models of phenotypic evolution is replaced by balancing selection. Expressions are provided for the equilibrium genetic variance in phenotype and for the heterozygosity. An approximate analysis of the transient properties of the model shows that, in certain circumstances, the behavior is quite similar to that of models based on the interaction of mutation and selection.
CONSERVED LINKAGE WITHIN A 4-cM REGION OF MOUSE CHROMOSOME 9 AND HUMAN CHROMOSOME 11
Authors: Antonucci T K , Von Deimling O H , Rosenblum B B , Skow L C , Meisler M H 
Published: January 2021

ABSTRACT
A six-point cross was carried out to determine the gene order and distances among loci on mouse chromosome 9. Our results are consistent with the following arrangement: centromere - Lap-1 - (1.2 ± 0.8) - Es-17 - (3.0 ± 1.0) - Ups - (1.3 ± 0.7) - Alp-1 - (23.1 ± 3.4) - Mod-1 - (10.9 ± 2.6) - Acy-1. This study provides the first estimate of the distances between Es-17, Ups and Alp-1. Exceptions to the preferred association of alleles of Es-17 and Ups have been found in three feral populations and one inbred strain. Evidence is presented for the homology of this chromosome region with the ESA4 - UPS - APO-AI region on the long arm of human chromosome 11.
ISOLATION AND CHARACTERIZATION OF CONDITIONAL ALLELES OF BACTERIOPHAGE T4 GENES uvsX AND uvsY
Authors: Conkling Mark A , Drake John W 
Published: January 2021

ABSTRACT
The bacteriophage T4 uvsW, uvsX and uvsY gene functions are required for wild-type levels of recombination and for normal survival and mutagenesis after treatments with ultraviolet (UV) and ionizing radiations. The ability of uvsX and uvsY mutations to suppress the lethality of gene 49 mutations was used to select temperature-sensitive and amber alleles of these two genes. (uvsW mutations do not suppress gene 49 mutations.) A simple and powerful complementation test was developed to assist in assigning uvs mutations to genes. The amber alleles of uvsX and uvsY behave as simple null alleles, fully suppressing a gene 49 defect, enhancing UV killing and abolishing UV mutagenesis. However, the properties of the ts alleles of uvsX and uvsY demonstrated that suppression of a gene 49 defect, sensitivity to UV-induced inactivation and UV mutability can be partially uncoupled. These results prompt the hypothesis that radiation mutagenesis occurs during DNA chain elongation past template damage within a recombinational intermediate rather than within a conventional replication fork.
DEVELOPMENTAL USE OF GENE PRODUCTS IN DROSOPHILA: THE MATERNAL-ZYGOTIC TRANSITION
Authors: Robbins Leonard G 
Published: January 2021

ABSTRACT
Recent results suggest that activity of a large fraction of the Drosophila genome is needed at multiple developmental stages. The timing of the transition from dependence on maternally stored gene products to reliance on zygotically coded products has been examined for several zygotic-lethal mutations in the z-w region of the X chromosome. The mutants differ in zygotic sensitivity to reduced maternal activity, and they have a wide range of times of lethality. Nevertheless, both temperature shift experiments and clonal analysis indicate that all of the maternal-zygotic transitions occur around the time of blastoderm formation.
EVOLUTION AND VARIATION OF RENIN GENES IN MICE
Authors: Dickinson Douglas P , Gross Kenneth W , Piccini Nina , Wilson Carol M 
Published: January 2021

ABSTRACT
Inbred strains of mice carry Ren-1, a gene encoding the thermostable Renin-1 isozyme. Ren-1 is expressed at relatively low levels in mouse submandibular gland and kidney. Some strains also carry Ren-2, a gene encoding the thermolabile Renin-2 isozyme. Ren-2 is expressed at high levels in the mouse submandibular gland and at very low levels, if at all, in the kidney. Ren-1 and Ren-2 are closely linked on mouse chromosome 1, show extensive homology in coding and noncoding regions and provide a model for studying the regulation of gene expression. An investigation of renin genes and enzymatic activity in wild-derived mice identified several restriction site polymorphisms as well as putative variants in renin gene expression and protein structure. The number of renin genes carried by different subpopulations of wild-derived mice is consistent with the occurrence of a gene duplication event prior to the divergence of M. spretus (2.75-5.5 million yr ago). This conclusion is in agreement with a prior estimate based upon comparative sequence analysis of Ren-1 and Ren-2 from inbred laboratory mice.
METAPHASE I ORIENTATION OF CHAIN-FORMING INTERCHANGE QUADRIVALENTS: A THEORETICAL CONSIDERATION
Authors: Koduru Prasad R K 
Published: January 2021

ABSTRACT
The orientation behavior of chain forming interchange quadrivalents at metaphase I was studied in three interchange heterozygotes of pearl millet [Pennisetum americanum (L.) Leeke] which involve chromosomes 1, 3, 6 and 7 in various combinations. Of these, two combinations predominantly produced rings and the third was a chain-forming type. The chain quadrivalents derived from the two ring-forming interchanges, as well as the chain quadrivalent generated by the third interchange, all showed one adjacent orientation at metaphase I (adjacent-1 or -2, depending upon the formation or failure of chiasmata and their positions in the different segments of the pachytene cross). Homologous centromere co-orientation leading to adjacent-1 and alternate-1 occurs following chiasma failure in the noncentric arms of the pachytene cross, and nonhomologous centromere co-orientation leading to adjacent-2 and alternate-2 occurs following chiasma failure in the centric arms of the pachytene cross. Thus, it has been proposed that, unlike in ring quadrivalents, a specific chain quadrivalent will have only homologous or nonhomologous centromere co-orientations at metaphase I.
DIRECTED FORMATION OF DELETIONS AND DUPLICATIONS USING Mud(Ap, lac)
Authors: Hughes Kelly T , Roth John R 
Published: January 2021

ABSTRACT
A genetic procedure is directed for the isolation of chromosomal deletions and duplications with predetermined endpoints. These rearrangements are generated in transduction crosses using a mixture of P22-transducing phage lysates grown on two strains, each carrying a Mud-lac insertion. The formation of duplications and deletions was demonstrated in the his operon using insertions of Mud1-8 (a transposition-defectiveMud-lac phage). This technique was also used to make larger chromosomal duplications between Mud1-8 insertions in the thr and leu biosynthetic operons and between Mud insertions in the thr and pyrB operons. Genetic evidence is presented that strongly suggests that inheritance of a single Mud prophage by P22-mediated crosses requires two transduced fragments; each carrying part of the Mud prophage. The two fragments must be involved in three recombinational exchanges; one exchange joins the donor Mud fragments and two exchanges occur between the composite fragment and the recipient chromosome, one on either side of the complete donor Mud element. Since duplications only occur between Mud insertions in the same orientation on the chromosome, the method of duplication formation provides a simple means of determining the orientation of Mud1-8 on the chromosome and, therefore, the direction of transcription of the gene into which Mud is inserted. This method was also used to construct recombinants between a Mud1-8 prophage and Casadaban's protein fusion vector Mud2 and, thereby, isolate Mud2-8, a Mud derivative containing the protein fusion ability of Mud2 and the defective transposition functions of Mud1-8.
MEIOTIC RECOMBINATION AND SPORULATION IN REPAIR-DEFICIENT STRAINS OF YEAST
Authors: Dowling Elizabeth L , Maloney Daniel H , Fogel Seymour 
Published: January 2021

ABSTRACT
A genetic system designed to monitor recombination and sporulation in various repair-deficient yeast strains was constructed. Variously heterozygous at seven or eight sites distributed across the genome, the system facilitated sensitive detection of changes in frequency or pattern of meiotic recombination. Ten rad mutants sensitive primarily to UV-irradiation and without terminal blocks in the sporulation process were studied. Seven were defective in excision repair (rad1, rad2, rad3, rad4, rad10, rad14 and rad16), and three were defective in mutagenic repair (rad5, rad9 and rad18). Individually, each mutant displayed behavior consistent with an orthodox meiosis including a wild-type meiotic recombination profile with respect to gene conversion, PMS and intergenic map distances. Accordingly, we conclude that these mutants are without major effect on meiotic heteroduplex formation or correction. However, certain combinations of excision-defective mutants with rad18 exhibited marked ascosporal inviability. Tetraploids homozygous for rad1 and rad18 produce a large proportion of diploid spores containing a recessive lethal.