Population differentiation and behavioural association of the two 'personality' genes DRD4 and SERT in dunnocks (Prunella modularis).

Quantifying the variation in behaviour-related genes within and between populations provides insight into how evolutionary processes shape consistent behavioural traits (i.e. personality). Deliberate introductions of non-native species offer opportunities to investigate how such genes differ between native and introduced populations and how polymorphisms in the genes are related to variation in behaviour. Here, we compared the genetic variation of the two 'personality' genes, DRD4 and SERT, between a native (United Kingdom, UK) and an introduced (New Zealand, NZ) population of dunnocks, Prunella modularis. The NZ population showed a significantly lower number of single nucleotide polymorphisms (SNPs) compared to the UK population. Standardized F'st estimates of the personality genes and neutral microsatellites indicate that selection (anthropogenic and natural) probably occurred during and post the introduction event. Notably, the largest genetic differentiation was found in the intronic regions of the genes. In the NZ population, we also examined the association between polymorphisms in DRD4 and SERT and two highly repeatable behavioural traits: flight-initiation distance and mating status (promiscuous females and cobreeding males). We found 38 significant associations (for different allele effect models) between the two behavioural traits and the studied genes. Further, 22 of the tested associations showed antagonistic allele effects for males and females. Our findings illustrate how introduction events and accompanying ecological changes could influence the genetic diversity of behaviour-related genes.

Population structure within an alpine archipelago: strong signature of past climate change in the New Zealand rock wren (Xenicus gilviventris).

Naturally subdivided populations such as those occupying high-altitude habitat patches of the 'alpine archipelago' can provide significant insight into past biogeographical change and serve as useful models for predicting future responses to anthropogenic climate change. Among New Zealand's alpine taxa, phylogenetic studies support two major radiations: the first correlating with geological forces (Pliocene uplift) and the second with climatic processes (Pleistocene glaciations). The rock wren (Xenicus gilviventris) is a threatened alpine passerine belonging to the endemic New Zealand wren family (Acanthisittidae). Rock wren constitute a widespread, naturally fragmented population, occurring in patches of suitable habitat over c. 900 m in altitude throughout the length of the South Island, New Zealand. We investigated the relative role of historical geological versus climatic processes in shaping the genetic structure of rock wren (N = 134) throughout their range. Using microsatellites combined with nuclear and mtDNA sequence data, we identify a deep north-south divergence in rock wren (3.7 ± 0.5% at cytochrome b) consistent with the glacial refugia hypothesis whereby populations were restricted in isolated refugia during the Pleistocene c. 2 Ma. This is the first study of an alpine vertebrate to test and provide strong evidence for the glacial refugia hypothesis as an explanation for the low endemicity central zone known as the biotic 'gap' in the South Island of New Zealand.

Postglacial expansion and not human influence best explains the population structure in the endangered kea (Nestor notabilis).

Inferring past demography is a central question in evolutionary and conservation biology. It is, however, sometimes challenging to infer the processes that shaped the current patterns of genetic variation in endangered species. Population substructuring can occur as a result of survival in several isolated refugia and subsequent recolonization processes or via genetic drift following a population decline. The kea (Nestor notabilis) is an endemic parrot widely distributed in the mountains of the South Island of New Zealand that has gone through a major human-induced population decline during the 1860s-1970s. The aims of this study were to understand the glacial and postglacial history of kea and to determine whether the recent population decline played a role in the shaping of the current genetic variation. We examined the distribution of genetic variation, differentiation and admixture in kea using 17 microsatellites and the mitochondrial control region. Mitochondrial data showed a shallow phylogeny and a genetic distinction between the North and South of the range consistent with the three genetic clusters identified with microsatellite data. Both marker types indicated an increase in genetic isolation by geographic distance. Approximate Bayesian Computation supported a scenario of postglacial divergence from a single ancestral glacial refugium, suggesting that the contemporary genetic structure has resulted from recolonization processes rather than from a recent population decline. The recent evolutionary origin of this genetic structure suggests that each genetic cluster does not need to be considered as independent conservation units.

Extensive variation at MHC DRB in the New Zealand sea lion (Phocarctos hookeri) provides evidence for balancing selection.

Marine mammals are often reported to possess reduced variation of major histocompatibility complex (MHC) genes compared with their terrestrial counterparts. We evaluated diversity at two MHC class II B genes, DQB and DRB, in the New Zealand sea lion (Phocarctos hookeri, NZSL) a species that has suffered high mortality owing to bacterial epizootics, using Sanger sequencing and haplotype reconstruction, together with next-generation sequencing. Despite this species' prolonged history of small population size and highly restricted distribution, we demonstrate extensive diversity at MHC DRB with 26 alleles, whereas MHC DQB is dimorphic. We identify four DRB codons, predicted to be involved in antigen binding, that are evolving under adaptive evolution. Our data suggest diversity at DRB may be maintained by balancing selection, consistent with the role of this locus as an antigen-binding region and the species' recent history of mass mortality during a series of bacterial epizootics. Phylogenetic analyses of DQB and DRB sequences from pinnipeds and other carnivores revealed significant allelic diversity, but little phylogenetic depth or structure among pinniped alleles; thus, we could neither confirm nor refute the possibility of trans-species polymorphism in this group. The phylogenetic pattern observed however, suggests some significant evolutionary constraint on these loci in the recent past, with the pattern consistent with that expected following an epizootic event. These data may help further elucidate some of the genetic factors underlying the unusually high susceptibility to bacterial infection of the threatened NZSL, and help us to better understand the extent and pattern of MHC diversity in pinnipeds.

The use of telomere length in ecology and evolutionary biology.

The measurement of telomere length (TL) is a genetic tool that is beginning to be employed widely in ecological and evolutionary studies as marker of age and fitness. The adoption of this approach has been accelerated by the development of telomere quantitative PCR, which enables the screening of large numbers of samples with little effort. However, the measurement and interpretation of TL change need to be done with a necessary level of rigour that has thus far often been missing where this approach has been employed in an ecological and evolutionary context. In this article, we critically review the literature available on the relationship between TL, age and fitness. We seek to familiarize geneticists, ecologists and evolutionary biologists with the shortcomings of the methods and the most common mistakes made while analysing TL. Prevention of these mistakes will ensure accuracy, reproducibility and comparability of TL studies in different species and allow the identification of ecological and evolutionary principles behind TL dynamics.

Demographic histories and genetic diversity across pinnipeds are shaped by human exploitation, ecology and life-history.

A central paradigm in conservation biology is that population bottlenecks reduce genetic diversity and population viability. In an era of biodiversity loss and climate change, understanding the determinants and consequences of bottlenecks is therefore an important challenge. However, as most studies focus on single species, the multitude of potential drivers and the consequences of bottlenecks remain elusive. Here, we combined genetic data from over 11,000 individuals of 30 pinniped species with demographic, ecological and life history data to evaluate the consequences of commercial exploitation by 18th and 19th century sealers. We show that around one third of these species exhibit strong signatures of recent population declines. Bottleneck strength is associated with breeding habitat and mating system variation, and together with global abundance explains much of the variation in genetic diversity across species. Overall, bottleneck intensity is unrelated to IUCN status, although the three most heavily bottlenecked species are endangered. Our study reveals an unforeseen interplay between human exploitation, animal biology, demographic declines and genetic diversity.

Electrophysiological evidence for a non-opioid interaction between dynorphin and GABA in the substantia nigra of the rat.

Interactions between neuronal responses mediated by dynorphin A1-8 and GABA were investigated in the substantia nigra zona reticulata. Extracellular recordings and microiontophoresis were performed using five-barrel microelectrodes in chloral hydrate-anesthetized male rats. When iontophoresed alone, dynorphin A1-Q significantly inhibited the firing of 22% of the neurons tested. The inhibition was rapid in onset and recovery and was dose-dependent. In another 22% of the cells, iontophoretic dynorphin produced an increase in the baseline firing rate which was slow in both onset and offset; the remaining 56% were unaffected by dynorphin. When GABA and dynorphin A1-8 were applied in conjunction, the inhibitory action of GABA was attenuated in 61% of the cells; whereas, when dynorphin and GABA were ejected simultaneously onto the cells that were inhibited by dynorphin A1-8, the respective inhibitory effects of dynorphin and GABA appeared to be additive. The kappa antagonist, MR-2266, failed to block the ability of dynorphin A1-8 to attenuate the action of GABA. In addition, the non-opiate peptide des-tyr-dynorphin A2-17, produced effects similar to that of dynorphin A1-8. The role of dynorphin in the basal ganglia and its interaction with the other major transmitter in the substantia nigra zona reticulata, GABA, is discussed.

High-energy ballistic and avulsive injuries. A management protocol for the next millennium.

This article discusses high-energy ballistic and avulsive injuries, which are a formidable challenge to the reconstructive surgeon. Management protocols are provided for the next millennium.

Limb salvage of lower-extremity wounds using free gracilis muscle reconstruction.

An extensive series reviewing the benefits and drawbacks of use of the gracilis muscle in lower-extremity trauma has not previously been collected. In this series of 50 patients, the use of microvascular free transfer of the gracilis muscle for lower-extremity salvage in acute traumatic wounds and posttraumatic chronic wounds is reviewed. In addition, the wound size, injury patterns, problems, and results unique to the use of the gracilis as a donor muscle for lower-extremity reconstruction are identified. In a 7-year period from 1991 to 1998, 50 patients underwent lower-extremity reconstruction using microvascular free gracilis transfer at the University of Maryland Shock Trauma Center, Johns Hopkins Hospital, and Johns Hopkins Bayview Medical Center. There were 22 patients who underwent reconstruction for coverage of acute lower-extremity traumatic soft-tissue defects associated with open fractures. The majority of patients were victims of high-energy injuries with 91 percent involving motor vehicle or motorcycle accidents, gunshot wounds, or pedestrians struck by vehicles. Ninety-one percent of the injuries were Gustilo type IIIb tibial fractures and 9 percent were Gustilo type IIIc. The mean soft-tissue defect size was 92.2 cm2. Successful limb salvage was achieved in 95 percent of patients. Twenty-eight patients with previous Gustilo type IIIb tibia-fibula fractures presented with posttraumatic chronic wounds characterized by osteomyelitis or deep soft-tissue infection. Successful free-tissue transfer was accomplished in 26 of 28 patients (93 percent). All but one of the patients in this group who underwent successful limb salvage (26 of 27, or 96 percent) are now free of infection. Use of the gracilis muscle as a free-tissue transfer has been shown to be a reliable and predictable tool in lower-extremity reconstruction, with a flap success and limb salvage rate comparable to those in other large studies.

Restoring abdominal wall integrity in contaminated tissue-deficient wounds using autologous fascia grafts.

Necrotizing abdominal wall infections, enteric fistulae, or exposed prosthetic material after ventral hernia repair often results in a loss of abdominal wall integrity. Further surgical reconstruction with prosthetic material is usually contraindicated in the contaminated wound because of the high infection rate necessitating prosthetic removal and further abdominal wall debridement. Consequently, for the past 9 years, we have been using free grafts of autologous fascia lata to replace deficient abdominal wall fascia and muscle in situations where prosthetic material is contraindicated and local tissue rearrangement (i.e., component separation) would be inadequate. Thirty-two patients (mean age 59 years) underwent abdominal wall reconstruction with autologous fascia lata grafts. Indications included exposed mesh (31 percent), enteric fistulae (28 percent), enteric contamination (22 percent), wound infection (13 percent), and immunosuppression alone (6 percent); 31 percent of all patients were immunosuppressed secondary to either a solid organ transplant or a systemic inflammatory disorder. Fascia grafts (mean size 10 x 17 cm) were sutured to the surrounding abdominal wall and covered by local skin flap advancement and/or myocutaneous flap rotation. All abdominal reconstructions were initially successful. Subsequent local abdominal wall complications included cellulitis (n = 3), seroma (n = 2), and skin dehiscence with exposed fascia grafts (n = 7). Five of seven patients with skin dehiscence healed by secondary intention, whereas two had split-thickness skin grafts successfully applied to the granulating fascia. Thigh donor site complications included hematoma (n = 1), skin dehiscence (n = 1), and seroma (n = 2). There have been no cases of lateral knee instability. The average follow-up period is 27 months (range 3 to 106 months). Recurrent hernia has been seen in three patients (9 percent). Interestingly, laparotomy has been performed through an intact fascia lata patch in three patients for unrelated intra-abdominal conditions. In each case, the graft was intact and revascularized, confirming experimental animal data performed in our laboratory. Recurrent hernia has not been observed through the laparotomy site. Our 9-year experience has demonstrated that in the face of large, contaminated abdominal wounds where prosthetic material is contraindicated and local tissue rearrangement would be inadequate, fascia lata autografts are a reliable adjuvant to abdominal wall reconstruction.

Traumatic optic neuropathy: a review of 61 patients.

The outcome of traumatic optic neuropathy was evaluated following penetrating and blunt injuries to assess the effect of treatment options, including high-dose steroids, surgical intervention, and observation alone. Factors that affected improvement in visual acuity were identified and quantified. Sixty-one consecutive, nonrandomized patients presenting with visual loss after facial trauma between 1984 and 1996 were assessed for outcome. Pretreatment and posttreatment visual acuities were compared using a standard ophthalmologic conversion from the values of no light perception, light perception, hand motion, finger counting, and 20/800 down to 20/15 to a logarithm of the minimum angle of resolution (log MAR). The percentage of patients showing visual improvement and the degree of improvement were calculated for each patient group and treatment method. Measurements of visual acuity are in log MAR units +/- standard error of the mean. Patients who sustained penetrating facial trauma (n = 21) had worse outcomes than patients with blunt trauma (n = 40). Improvement in visual acuity after treatment was seen in 19 percent of patients with penetrating trauma compared with 45 percent of patients with blunt trauma (p < 0.05). Furthermore, patients with penetrating trauma improved less than those with blunt trauma, with a mean improvement of 0.4 +/- 0.23 log MAR compared with 1.1 +/- 0.24 in blunt-trauma patients (p = 0.03). The patients with blunt trauma underwent further study. There was no significant difference in improvement of visual acuity in patients treated with surgical versus nonsurgical methods; however, 83 percent of patients without orbital fractures had improvement compared with 38 percent of patients with orbital fractures (p < 0.05). The mean improvement in patients without orbital fractures was 1.8 +/- 0.65 log MAR compared with 0.95 +/- 0.26 in patients with orbital fractures (p = 0.1). Twenty-seven percent of patients who had no light perception on presentation experienced improvement in visual acuity after treatment compared with 100 percent of patients who had light perception on admission (p < 0.05). The mean improvement in patients who were initially without light perception was 0.85 +/- 0.29 log MAR compared with 1.77 +/- 0.35 in patients who had light perception (p < 0.05). There were no significant differences in improvement of visual acuity when analyzing the effect of patient age and timing of surgery. Patients who sustain penetrating trauma have a worse prognosis than those with blunt trauma. The presence of no light perception and an orbital fracture are poor prognostic factors in visual loss following blunt facial trauma. It seems that clinical judgment on indication and timing of surgery, and not absolute criteria, should be used in the management of traumatic optic neuropathy.

Craniofacial distraction osteogenesis: a review of 3278 cases.

The nascent field of craniofacial distraction osteogenesis has not yet been subjected to a rigorous evaluation of techniques and outcomes. Consequently, many of the standard approaches to distraction have been borrowed from the experience with long bones in orthopedic surgery. The ideal "latency period" of neutral fixation, rate and rhythm of distraction, and consolidation period have not yet been determined for the human facial skeleton. In addition, because the individual craniofacial surgeon's experience with distraction has generally been small, outcomes and meaningful complication rates have not yet been published. In this study, a four-page questionnaire was sent to 2476 craniofacial and oral/maxillofacial surgeons throughout the world, asking about their experiences with distraction osteogenesis. Information about the types of cases, indications for surgery, surgical techniques, postoperative management, outcomes, and complications were tabulated. Of 274 respondents (response rate, 11.4 percent), 148 indicated that they used distraction in their surgical practice. One hundred forty-five completed surveys were entered into a database that provided information about 3278 craniofacial distraction cases. Statistical analyses were performed comparing the rates of premature consolidation, fibrous nonunion, and nerve injury, on the basis of the use of a latency period and different rates and rhythms of distraction. In addition, the rates of all complications were determined and compared on the basis of the number of distraction cases performed per surgeon. The results of the study clearly show a wide variation in the surgical practice of craniofacial distraction osteogenesis. Although the cumulative complication rate was found to be 35.6 percent, there is a pronounced learning curve, with far fewer complications occurring among more experienced surgeons (p < 0.001). The presence of inferior alveolar nerve injury as a result of mandibular distraction was much lower for respondents whose distraction regimens consisted of no more than 1 mm of distraction per day (19.5 percent versus 2.4 percent; p < 0.001). No evidence was found to support the use of a latency period or to divide the daily distraction regimen into more than one session per day. Conclusions could not be drawn from this study regarding the length of the consolidation period. Overall, the surgeon-reported outcomes are comparable with those published for other craniofacial procedures, despite the higher incidence of complications. Although conclusions made on the basis of a subjective questionnaire need to be interpreted cautiously, this study has strength in the large numbers of cases reviewed. Because of the anonymity of responses, it has been assumed that surgeons who responded to the survey reported accurate numbers of complications and successful outcomes. Finally, additional clinical and animal studies that will be of benefit in advancing the field of craniofacial distraction osteogenesis are outlined.

A prescription model for peritoneal dialysis.

The authors have developed a mathematical model for peritoneal dialysis, based on the Popovich-Pyle-Moncrief approach, that is capable of predicting urea Kt/V and total weekly creatinine clearance for a variety of peritoneal dialysis therapies. This prescription model incorporates both diffusive and convective solute removal as well as ultrafiltration and lymphatic absorption. The primary input to the model is a single peritoneal equilibration test. Twenty-four hour dialysate collection is not required. Results from an extensive prospective clinical study performed with 100 patients at five dialysis centers indicate that the model is valid for predicting urea Kt/V and creatinine clearance for continuous ambulatory peritoneal dialysis and continuous cycling peritoneal dialysis. Predicted clearances agree with the clinical data from these patients to within an average difference of approximately 10%. This model promises to be a powerful tool to assist nephrologists in quantifying the amount of peritoneal dialysis delivered by a given prescription, tailoring it to individual patient needs, and investigating the potential efficacy of a variety of alternative therapies.

Initial clinical experience with a new model of mass transfer for peritoneal dialysis.

A clinical pilot study compared predictions of a new model of peritoneal dialysis mass transfer to measured weekly KT/V urea (KTu/V) and weekly creatinine clearance (Ccr) in liters per 1.73 m2 in 50 patients from five centers (40 CAPD, 10 CCPD). The Robertson et al. model is unique in that it does not require a 24-hour collection of dialysate. Instead, model predictions are based on the results of a standard 4-hour peritoneal equilibration test (PET) and appropriate demographic data. Analysis revealed 12 collection errors, 8 affecting the PET and 4 affecting 24-hour dialysate volume. PET drainage volume was low in six cases, excessive in two; 24-hour volume was incomplete in three, excessive in one. Similar errors were not found in the remaining 38 patients. In the 38 patients with correctly performed PET and dialysate collections, agreement between predicted and measured values was excellent.

2-Deoxyribose gene-enzyme complex in Salmonella typhimurium: regulation of phosphodeoxyribomutase.

Phosphodeoxyribomutase, the enzyme which catalyzes the interconversion of 2-deoxyribose-1-phosphate to 2-deoxyribose-5-phosphate, has been partially purified from Salmonella typhimurium. The enzyme had an absolute requirement for manganese ion and was stimulated by glucose-1, 6-diphosphate. Phosphodeoxyribomutase was induced by deoxyribose-5-phosphate and was coordinately regulated with the enzymes thymidine phosphorylase and deoxyribose-5-phosphate aldolase, type II. Mutants deficient in these three enzymes were isolated and mapped close to the threonine locus in S. typhimurium. The three enzymes thymidine phosphorylase, deoxyribose-5-phosphate aldolase, type II, and phosphodeoxyribomutase are controlled by a series of linked genes and appear to constitute an operon.

Effects of EPO therapy on backfiltration of dialysate in high flux dialysis.

The authors have developed a comprehensive mathematical model of the hemodialysis process to investigate the effect of r-HuEPO and the accompanying higher hematocrit on backfiltration in high flux dialysis. Model simulations indicate that under otherwise identical conditions typical of high flux dialysis, an increase in hematocrit from 20 to 33% will increase the amount of dialysate fluid entering the blood from 2.4 L to 3.8 L in a 4 hr treatment. We used the mathematical model to investigate the effect of the following variables on backfiltration: blood flow rate, ultrafiltration rate, inside fiber diameter, fiber length, and membrane permeability. While increasing the blood flow rate may enhance solute transport, it was found to increase backfiltration substantially through its effect on the axial pressure drop. This effect was most pronounced at the higher hematocrits due to the higher viscosity. It was found that increasing the fiber ID, decreasing the fiber length, and decreasing the permeability of the membrane (all at constant surface area) could be beneficial in reducing backfiltration. However, these results do not consider the potential negative impact of these changes on solute clearance. Finally, the mathematical model enhanced our understanding of the transport processes governing backfiltration. Due to protein concentration gradients in the lumen, protein osmotic pressures as high as 50-100 mmHg can be obtained in high-flux dialysis. As a result, providing an outlet hydrostatic blood pressure greater than the inlet hydrostatic dialysate pressure is not sufficient to guarantee the absence of backfiltration.

The occipital bar and internal osteotomies in the treatment of lambdoidal synostosis.

Lambdoidal synostosis results in unilateral or bilateral deformities. Patients with this diagnosis often present with moderate to severe deformities at a relatively late period in development. This late presentation limits the options for treatment and methods for correction. Occipital bar advancement and internal osteotomies provide an accurate, reliable, and quantitative method to treat the deformity. This technique addresses the variable degree of asymmetry and the large flattened bony segments. It was performed in 12 patients over 18 months, with good to excellent results.

Genetic regulation of ribonucleoside and deoxyribonucleoside catabolism in Salmonella typhimurium.

Four enzymes involved in ribonucleoside and deoxyribonucleoside catabolism (deoxyribose-5-P aldolase, thymidine phosphorylase, phosphodeoxyribomutase, and purine nucleoside phosphorylase) are coded for by four closely linked structural genes on the Salmonella chromosome. The genetic order of these genes is (deoC-deoA-deoB-deoD)-serB-thr. Studies on polarity mutants and induction patterns indicate that the deoB and deoD genes may constitute a single operon and that the deoC and deoA genes may constitute a second closely linked operon.

Transverse glabellar flap for obliteration/isolation of the nasofrontal duct from the anterior cranial base.

Management of fractures involving the nasofrontal duct region of the frontal sinus has focused on preserving function when possible or obliterating the sinus and duct when fracture patterns potentiate ductal obstruction and possible transcranial seeding of bacteria. When frontal sinus preservation is in doubt, controversy surrounds the use of cranialization versus obliteration, and the method of obliteration. Perioperative and late postoperative infections are uncommon, but their occurrence jeopardizes an often complex reconstruction and can be life threatening. This paper describes the design and indications for a pedicled transverse glabellar muscle flap for obliteration of the nasofrontal duct, thereby isolating the anterior cranial base from the aerodigestive system. This vascularized muscle flap utilizes the corrugator supercilii and procerus muscles, which are introduced into the sinus via a small, surgically created window in the superomedial orbital wall without disturbing the central facial aesthetic contours. Six patients with comminuted fractures at the nasofrontal duct level associated with displaced posterior frontal sinus fractures have been treated with the transverse glabellar flap. Follow-up ranges from 8 to 30 months. There have been no early or late postoperative complications. The transverse glabellar flap is a reliable and versatile method of partitioning the upper aerodigestive tract from the anterior cranial base with vascularized tissue, thus minimizing the risk of infectious complications. The resulting donor site deformity is more acceptable than that seen with the traditional pedicled galeal frontalis flap.