bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of Gene Amplification to Evolution of Increased Antibiotic Resistance inSalmonella typhimurium
Authors: Sun Song , Berg Otto G , Roth John R , Andersson Dan I 
Published: May 2009

AbstractThe use of β-lactam antibiotics has led to the evolution and global spread of a variety of resistance mechanisms, including β-lactamases, a group of enzymes that degrade the β-lactam ring. The evolution of increased β-lactam resistance was studied by exposing independent lineages of Salmonella typhimurium to progressive increases in cephalosporin concentration. Each lineage carried a β-lactamase gene (blaTEM-1) that provided very low resistance. In most lineages, the initial response to selection was an amplification of the blaTEM-1 gene copy number. Amplification was followed in some lineages by mutations (envZ, cpxA, or nmpC) that reduced expression of the uptake functions, the OmpC, OmpD, and OmpF porins. The initial resistance provided by blaTEM-1 amplification allowed the population to expand sufficiently to realize rare secondary point mutations. Mathematical modeling showed that amplification often is likely to be the initial response because events that duplicate or further amplify a gene are much more frequent than point mutations. These models show the importance of the population size to appearance of later point mutations. Transient gene amplification is likely to be a common initial mechanism and an intermediate in stable adaptive improvement. If later point mutations (allowed by amplification) provide sufficient adaptive improvement, the amplification may be lost.
Evolution of Stochastic Switching Rates in Asymmetric Fitness Landscapes
Authors: Salathé Marcel , Van Cleve Jeremy , Feldman Marcus W 
Published: May 2009

Abstract
Uncertain environments pose a tremendous challenge to populations: The selective pressures imposed by the environment can change so rapidly that adaptation by mutation alone would be too slow. One solution to this problem is given by the phenomenon of stochastic phenotype switching, which causes genetically uniform populations to be phenotypically heterogenous. Stochastic phenotype switching has been observed in numerous microbial species and is generally assumed to be an adaptive bet-hedging strategy to anticipate future environmental change. We use an explicit population genetic model to investigate the evolutionary dynamics of phenotypic switching rates. We find that whether or not stochastic switching is an adaptive strategy is highly contingent upon the fitness landscape given by the changing environment. Unless selection is very strong, asymmetric fitness landscapes—where the cost of being maladapted is not identical in all environments—strongly select against stochastic switching. We further observe a threshold phenomenon that causes switching rates to be either relatively high or completely absent, but rarely intermediate. Our finding that marginal changes in selection pressures can cause fundamentally different evolutionary outcomes is important in a wide range of fields concerned with microbial bet hedging.
Global Analysis of Allele-Specific Expression in Arabidopsis thaliana
Authors: Zhang Xu , Borevitz Justin O 
Published: May 2009

Abstract
Gene expression is a complex trait determined by various genetic and nongenetic factors. Among the genetic factors, allelic difference may play a critical role in gene regulation. In this study we globally dissected cis (allelic) and trans sources of genetic variation in F1 hybrids between two Arabidopsis thaliana wild accessions, Columbia (Col) and Vancouver (Van), using a new high-density SNP-tiling array. This array tiles the whole genome with 35-bp resolution and interrogates 250,000 SNPs identified from resequencing of 20 diverse A. thaliana strains. Quantitative assessment of 12,311 genes identified 3811 genes differentially expressed between parents, 1665 genes with allele-specific expression, and 1688 genes controlled by composite trans-regulatory variation. Loci with cis- or trans-regulatory variation were mapped onto sequence polymorphisms, epigenetic modifications, and transcriptional specificity. Genes regulated in cis tend to be located in polymorphic chromosomal regions, are preferentially associated with repressive epigenetic marks, and exhibit high tissue expression specificity. Genes that vary due to trans regulation reside in relatively conserved chromosome regions, show activating epigenetic marks and generally constitutive gene expression. Our findings demonstrate a method of global functional characterization of allele-specific expression and highlight that chromatin structure is intertwined with evolution of cis- and trans-regulatory variation.
Analysis of Pax6 Contiguous Gene Deletions in the Mouse, Mus musculus, Identifies Regions Distinct from Pax6 Responsible for Extreme Small-Eye and Belly-Spotting Phenotypes
Authors: Favor Jack , Bradley Alan , Conte Nathalie , Janik Dirk , Pretsch Walter , Reitmeir Peter , Rosemann Michael , Schmahl Wolfgang , Wienberg Johannes , Zaus Irmgard 
Published: May 2009

Abstract
In the mouse Pax6 function is critical in a dose-dependent manner for proper eye development. Pax6 contiguous gene deletions were shown to be homozygous lethal at an early embryonic stage. Heterozygotes express belly spotting and extreme microphthalmia. The eye phenotype is more severe than in heterozygous Pax6 intragenic null mutants, raising the possibility that deletions are functionally different from intragenic null mutations or that a region distinct from Pax6 included in the deletions affects eye phenotype. We recovered and identified the exact regions deleted in three new Pax6 deletions. All are homozygous lethal at an early embryonic stage. None express belly spotting. One expresses extreme microphthalmia and two express the milder eye phenotype similar to Pax6 intragenic null mutants. Analysis of Pax6 expression levels and the major isoforms excluded the hypothesis that the deletions expressing extreme microphthalmia are directly due to the action of Pax6 and functionally different from intragenic null mutations. A region distinct from Pax6 containing eight genes was identified for belly spotting. A second region containing one gene (Rcn1) was identified for the extreme microphthalmia phenotype. Rcn1 is a Ca+2-binding protein, resident in the endoplasmic reticulum, participates in the secretory pathway and expressed in the eye. Our results suggest that deletion of Rcn1 directly or indirectly contributes to the eye phenotype in Pax6 contiguous gene deletions.
Linking “Sink or Swim” Indicators to Delayed Mortality in Red Snapper by Using a Condition Index
Authors: Diamond Sandra L. , Campbell Matthew D. 
Published: May 2009

Abstract
The ability of fish to submerge after discarding is often used as a proxy for survival, but this practice underestimates total discard mortality because delayed mortality is overlooked. Fishery managers need a way to link “sink or swim” indicators, or variables observed during capture and release, with delayed mortality rates. We conducted a cage study of red snapper Lutjanus campechanus off the coast of Texas to estimate delayed mortality rates and to find factors that could link immediate and delayed mortality. Immediate mortality (17%) was predicted by the interaction of depth and the difference in temperature between surface and bottom waters. Lactate levels were also significant predictors of immediate mortality in fish whose blood was tested. Delayed mortality (64%) was predicted primarily by a condition index consisting of the presence or absence of injuries, symptoms of barotrauma, and fish behaviors immediately after capture. Specific categories included bleeding, protruding intestines, everted stomach, exopthalmia, the presence or absence of flapping and gilling behaviors, and problems with cage submergence. The majority of fatalities occurred within 24 h after fish were placed in the cages. Our mortality estimates indicate that red snapper discard mortality was significantly underestimated in the 2005 stock assessment for red snapper. The use of indices that relate the condition of an individual fish at capture to its probability of delayed mortality is an excellent method for linking immediate and delayed mortality and will likely be applicable to many species that are subject to catch-and-release fishing.
Barging Effects on Sensory Systems of Chinook Salmon Smolts
Authors: Halvorsen Michele B. , Wysocki Lidia E. , Stehr Carla M. , Baldwin David H. , Chicoine David R. , Scholz Nathaniel L. , Popper Arthur N. 
Published: May 2009

AbstractTo avoid mortality caused by passage through dam turbines and spillways, juvenile Chinook salmon Oncorhynchus tshawytscha are annually transported downstream by barge through the federal hydropower system on the Snake and Columbia rivers. Survival of transported fish is higher than that of in‐river migrants; however, transported fish experience higher rates of postrelease mortality. Increased mortality could result from a decrease in the ability to detect or avoid predators due to stressors associated with the barge environment. This study examined the effects of barging on juvenile Chinook salmon olfaction and auditory function, two sensory systems involved in predator detection. We focused on dissolved metals known to be toxic to the salmon olfactory system and on the level of noise from the barge, which could impair the auditory system. Experimental groups included animals collected (1) before barge loading (control group), (2) at the Bonneville Dam bypass system (migrant fish), (3) immediately after barge transport, and (4) within 7 d postbarging and at or after 7 d postbarging. Measured concentrations of dissolved metals from the water within the barge were below established water quality criteria for the protection of aquatic life. Moreover, ultrastructural examination of the olfactory epithelium surface showed no evidence of injury to olfactory sensory neurons. Noise in the barge holding tanks had levels up to 136 dB referenced to 1 μPa (root mean square) with primary energy below 400 Hz. Auditory sensitivity was measured using the auditory‐evoked potentials (AEP) technique. We found a small but statistically significant threshold shift for fish collected within 7 d postbarging, while in the 7‐d‐and‐later postbarging group the AEP thresholds were similar to the control. Our findings indicate that the olfactory systems of transported Chinook salmon are intact and probably functional, while the auditory sensitivities are compromised with probable recovery.
Evolutionary Ecology of Redband Trout
Authors: Currens Kenneth P. , Schreck Carl B. , Li Hiram W. 
Published: May 2009

AbstractWe examined genetic differences at 29 enzyme encoding loci among 10,541 rainbow trout Oncorhynchus mykiss from 240 collections throughout the species' range, including redband trout (i.e., several rainbow trout subspecies) in pluvial lake basins of the northern Great Basin that have had largely internal drainage with no connection to the Pacific Ocean. Differences among groups accounted for 29.2% of the genetic variation. Although we observed major genetic differences between coastal and inland groups (10.7%), which are currently considered to represent the major phylogenetic division in the species, we found that the greatest evolutionary divergence (19.7%) was related to persistence of three major river systems: The upper Sacramento, Klamath, and Columbia rivers. Genetic traits of redband trout from the northern Great Basin, where we found distinct subspecies or races, indicated that over millennia these pluvial habitats were sources of evolutionary diversity associated with large river systems rather than completely isolated refugia. However, redband trout did not constitute a distinct monophyletic group. Based on our data, redband trout of the Goose Lake, Warner Valley, and Chewaucan basins were distinct genetic races that were part of the diverse complex of Sacramento redband trout O. mykiss stonei. Harney Basin redband trout were a unique genetic race most closely associated with Columbia River redband trout O. mykiss gairdneri. White River and Fort Rock redband trout were associated with the Columbia River but showed allelic divergence comparable with that among other subspecies. Upper Klamath Lake rainbow trout included a previously unrecognized group associated with populations in the headwaters of the basin and a different subspecies from type locations for Upper Klamath Lake redband trout O. mykiss newberrii (i.e., Upper Klamath Lake and the upper Klamath River). The relationship of redband trout from the Catlow Valley to any of these other groups remained unresolved.
Cetuximab and Other Anti–Epidermal Growth Factor Receptor Monoclonal Antibodies in the Treatment of Non-Small Cell Lung Cancer
Authors: Gridelli Cesare , Maione Paolo , Ferrara Marianna Luciana , Rossi Antonio 
Published: May 2009

Learning Objectives
Classify clinical and molecular predictors of outcomes of anti-EGFR monoclonal antibodies. Appraise the clinical results of anti-EGFR monoclonal antibodies in the treatment of patients with NSCLC. Assess the clinical results of therapy with anti-EGFR monoclonal antibodies combined with other new biologic agents in the treatment of patients with NSCLC.
This article is available for continuing medical education credit at CME.TheOncologist.com
Bortezomib-Induced Lupus Erythematosus Tumidus
Authors: Böckle Barbara C. , Baltaci Mehmet , Weyrer Walpurga , Sepp Norbert T. 
Published: May 2009

Abstract
This paper reports on an exceptional case of lupus erythematosus tumidus induced by bortezomib during the treatment of multiple myeloma.
Dying at the Right Time: A Modern Dilemma
Authors: van Laarhoven Hanneke W.M. , Leget Carlo J.W. , van der Graaf Winette T.A. 
Published: May 2009

Abstract
This article reflects on the motives behind the decision of medical oncologists to aggressively treat, with the goal of a possible cure, a critically ill cancer patient who initially refused treatment because he was “ready to die.”
Early repeat surgery for persistent Cushing's disease
Authors: Ram Zvi , Nieman Lynnette K. , Cutler Gordon B. , Chrousos George P. , Doppman John L. , Oldfield Edward H. 
Published: May 2009

✓ The potential efficacy of early repeat transsphenoidal surgery for persistent Cushing's disease has not previously been examined. On 222 patients with no prior pituitary treatment and a preoperative diagnosis of Cushing's disease, 29 (13%) remained hypercortisolemic after an initial transsphenoidal pituitary exploration. Seventeen of these 29 patients underwent further surgery 7 to 46 days after the initial transsphenoidal approach in order to completely excise suspected residual tumor. Patients were followed for 4 to 84 months (mean ± standard deviation, 34 ± 25 months) to document sustained remission or recurrence of Cushing's disease (a urine free cortisol level > 90 µg/day was considered evidence of recurrence).
Of the 17 patients with repeat surgery, 12 (71%) had resolution of hypercortisolism (morning plasma cortisol level < 5 µg/dl); however, in three of these 12, hypercortisolism recurred 5, 12, and 24 months later. In 14 patients a lesion that appeared to be a tumor was identified during the initial procedure or on histological examination. Of these, 12 had immediate resolution of hypercortisolism and nine are still in remission. Three patients, in whom no adenoma could be identified during the initial surgery or an examination of the partial hypophysectomy specimen from the initial surgery, had persistent Cushing's syndrome after the second operation. Seven (41%) of the 17 patients developed hypopituitarism requiring treatment with thyroid hormone, gonadal steroid, or vasopressin replacement.
The low incidence of identification of an adenoma on computerized tomography or magnetic resonance images (three of 17 patients), the failure to find a corticotrophic adenoma during the initial surgery (10 of 17 patients), and the failure of these 17 patients to respond to the initial transsphenoidal surgery suggest that they may comprise a subset of patients who are more difficult to treat successfully with surgery than most patients with Cushing's disease. Despite that, early reoperation induced immediate remission of hypercortisolism in 71% of cases, but did so at the expense of a high risk of hypopituitarism. However, since the alternative treatments (such as radiation therapy, long-term drug therapy, or bilateral adrenalectomy) also have potential adverse effects, early reoperation deserves consideration for the management of persistent Cushing's disease, especially when an adrenocorticotrophic hormone-secreting adenoma was partially excised during the first surgery.
Role of intracranial pressure monitoring in severely head-injured patients without signs of intracranial hypertension on initial computerized tomography
Authors: O'Sullivan Michael G. , Statham Patrick F. , Jones Patricia A. , Miller J. Douglas , Dearden N. Mark , Piper Ian R. , Anderson Shirley I. , Housley Alma , Andrews Peter J. , Midgley Susan , Corrie Jane , Tocher Janice I. , Sellar Robin 
Published: May 2009

✓ Previous studies have suggested that only a small proportion (< 15%) of comatose head-injured patients whose initial computerized tomography (CT) scan was normal or did not show a mass lesion, midline shift, or abnormal basal cisterns develop intracranial hypertension. The aim of the present study was to re-examine this finding against a background of more intensive monitoring and data acquisition.
Eight severely head-injured patients with a Glasgow Coma Scale score of 8 or less, whose admission CT scan did not show a mass lesion, midline shift, or effaced basal cisterns, underwent minute-to-minute recordings of arterial blood pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) derived from blood pressure minus ICP. Intracranial hypertension (ICP ≥ 20 mm Hg lasting longer than 5 minutes) was recorded in seven of the eight patients; in five cases the rise was pronounced in terms of both magnitude (ICP ≥ 30 mm Hg) and duration. Reduced CPP (≤ 60 mm Hg lasting longer than 5 minutes) was recorded in five patients.
Severely head-injured (comatose) patients whose initial CT scan is normal or does not show a mass lesion, midline shift, or abnormal cisterns nevertheless remain at substantial risk of developing significant secondary cerebral insults due to elevated ICP and reduced CPP. The authors recommend continuous ICP and blood pressure monitoring with derivation of CPP in all comatose head-injured patients.
The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord injury in rats
Authors: Constantini Shlomo , Young Wise 
Published: May 2009

✓ Recent clinical trials have reported that methylprednisolone sodium succinate (MP) or the monosialic ganglioside GM1 improves neurological recovery in human spinal cord injury. Because GM1 may have additive or synergistic effects when used with MP, the authors compared MP, GM1, and MP+GM1 treatments in a graded rat spinal cord contusion model. Spinal cord injury was caused by dropping a rod weighing 10 gm from a height of 1.25, 2.5, or 5.0 cm onto the rat spinal cord at T-10, which had been exposed via laminectomy. The lesion volumes were quantified from spinal cord Na and K shifts at 24 hours after injury and the results were verified histologically in separate experiments. A single dose of MP (30 mg/kg), given 5 minutes after injury, reduced 24-hour spinal cord lesion volumes by 56% (p = 0.0052), 28% (p = 0.0065), and 13% (p > 0.05) in the three injury-severity groups, respectively, compared to similarly injured control groups treated with vehicle only. Methylprednisolone also prevented injury-induced hyponatremia and increased body weight loss in the spine-injured rats. When used alone, GM1 (10 to 30 mg/kg) had little or no effect on any measured variable compared to vehicle controls; when given concomitantly with MP, GM1 blocked the neuroprotective effects of MP. At a dose of 3 mg/kg, GM1 partially prevented MP-induced reductions in lesion volumes, while 10 to 30 mg/kg of GM1 completely blocked these effects of MP. The effects of MP on injury-induced hyponatremia and body weight loss were also blocked by GM1. Thus, GM1 antagonized both central and peripheral effects of MP in spine-injured rats.Until this interaction is clarified, the authors recommend that MP and GM1 not be used concomitantly to treat acute human spinal cord injury. Because GM1 modulates protein kinase activity, protein kinases inhibit lipocortins, and lipocortins mediate anti-inflammatory effects of glucocorticoids, it is proposed that the neuroprotective effects of MP are partially due to anti-inflammatory effects and that GM1 antagonizes the effects of MP by inhibiting lipocortin. Possible beneficial effects of GM1 reported in central nervous system injury may be related to the effects on neural recovery rather than acute injury processes.
Experimental model of posttraumatic syringomyelia: the role of adhesive arachnoiditis in syrinx formation
Authors: Cho Ki Hong , Iwasaki Yoshinobu , Imamura Hiroyuki , Hida Kazutoshi , Abe Hiroshi 
Published: May 2009

✓ An experimental model was devised to elucidate the role of spinal blockade in posttraumatic syringomyelia. Thirty-eight Japanese White rabbits, each weighing about 3 kg, were used in this study. The animals were divided into four groups: in Group 1, eight animals received traumatic injury only; in Group 2, 12 animals received traumatic injury following injection of 100 mg kaolin suspended in 1 cc normal saline solution into the subarachnoid space at the site of trauma; in Group 3, nine animals received traumatic injury following injection of 200 mg kaolin in 1 cc normal saline solution into the subarachnoid space at the site of trauma; and in Group 4, nine animals without traumatic injury received an injection of 200 mg kaolin in 1 cc normal saline solution into the subarachnoid space.
The subjective criteria for syrinx formation were the presence of a definite round cyst having a smooth margin and an upper or lower extension of more than 2 cm from the injured site. Syrinx formation was seen in 12.5% (one of eight rabbits) in Group 1, 41.7% (five of 12 animals) in Group 2, 55.5% (five of nine rabbits) in Group 3 and 0% (none of nine animals) in Group 4 (p < 0.05). There was a tendency for the combined trauma/kaolin injection groups to be more prone to develop a syrinx. In the kaolin injection only group (Group 4), no animal showed a definite cyst or an extending cavity during the experimental period. The results suggest that kaolin enhances the extension of multiple small cavities that have already formed at the time of initial injury. The difference between the frequency of syrinx formation and the time of survival was statistically significant well beyond the 0.05% level. The overall difference, relating to the frequency of syrinx development, group, and duration of survival, was also statistically significant. In summary, subarachnoid block secondary to adhesive arachnoiditis is important in initiating the extension of the syringomyelia cavity.