bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose control in diabetes: which target level to aim for?
Authors: Laakso M. , Cederberg H. 
Published: February 2012

Abstract.  Laakso M, Cederberg H (University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland). Glucose control in diabetes: which target level to aim for? (Reveiw). J Intern Med 2012; 272: 1–12.The most important goal in the treatment of patients with diabetes is to lower the risk of long‐term diabetes complications. Hyperglycaemia is the most important risk factor for microvascular complications in diabetes, but, in addition to hyperglycaemia, several other risk factors, particularly dyslipidaemia, elevated blood pressure and smoking, also determine the risk of macrovascular complications. In this review, we present evidence from longitudinal population‐based studies that hyperglycaemia is an important risk factor for long‐term complications of diabetes and discuss the results from clinical trials of the effects of the treatment of hyperglycaemia on the prevention of long‐term micro‐ and macrovascular complications in type 1 and type 2 diabetes. An HbA1c target of <7.0% for the treatment of diabetes is generally accepted on the basis of evidence from several trials, whereas a target of <6.5% may be reasonable for patients with a short duration of type 2 diabetes and without extensive atherosclerosis.
Phylogeography of a Tertiary relict plant, Meconopsis cambrica (Papaveraceae), implies the existence of northern refugia for a temperate herb
Authors: VALTUEÑA FRANCISCO J. , PRESTON CHRIS D. , KADEREIT JOACHIM W. 
Published: February 2012

AbstractThe perennial herb Meconopsis cambrica, a western European endemic, is the only European species of the otherwise Himalayan genus Meconopsis and has been interpreted as a Tertiary relict species. Using rbcL and ITS sequence variation, we date the split between M. cambrica and its sister clade Papaver s.str. to the Middle to Upper Miocene (12.8 Myr, 6.4–19.2 Myr HPD). Within M. cambrica, cpDNA sequence variation reveals the existence of two groups of populations with a comparable level of genetic variation: a northern group from Great Britain, the Massif Central, the western Pyrenees and the Iberian System, and a southern group from the central and eastern Pyrenees. Populations from the Cantabrian Mountains were placed in both groups. Based on ITS sequence variation, the divergence between these two groups can be dated to 1.5 Myr (0.4–2.8 Myr HPD), and the age of the British populations is estimated as 0.37 Myr (0.0–0.9 Myr HPD). Amplified fragment length polymorphism results confirm the distinctive nature of the populations from Britain, the Massif Central and the central and eastern Pyrenees. These patterns of latitudinal variation of M. cambrica differ from patterns of longitudinal differentiation found in many other temperate species and imply glacial survival of the northern populations in northerly refugia. The primary differentiation into northern and southern cpDNA groups dates to near the onset of the Quaternary and suggests that an ancient phylogeographic pattern has survived through several glacial periods. Our data provide evidence that the species has persisted for a long period with a highly fragmented and probably very localized distribution.
Kin selection may contribute to lek evolution and trait introgression across an avian hybrid zone
Authors: CONCANNON MOIRA R. , STEIN ADAM C. , UY J. ALBERT C. 
Published: February 2012

AbstractUnderstanding the mechanism(s) that favour cooperation among individuals competing for the same resources provides direct insights into the evolution of grouping behaviour. In a hybrid zone between golden‐/yellow‐collared (Manacus vitellinus) and white‐collared (Manacus candei) manakins, males form aggregations composed of white and yellow males solely to attract females (‘mixed leks’). Previous work shows that yellow males in these mixed leks experience a clear mating advantage over white males, resulting in the preferential introgression of yellow plumage allele(s) into the white species. However, the yellow male mating advantage only occurs in mixed leks with high frequencies of yellow males, and only a few of these males probably mate. Hence, it remains unclear why unsuccessful males join leks. Here, we used microsatellite markers to estimate pairwise relatedness among males within and between leks to test whether indirect genetic benefits of helping kin (‘kin selection’) can promote grouping. We found that yellow males are significantly more related to each other within than between leks, while relatedness among white males did not differ within and between leks. This suggests that yellow males may indirectly enhance their own reproductive success by preferentially lekking with relatives because yellow plumage is under positive frequency‐dependent selection (positive FDS). Our results are consistent with the hypothesis that kin selection may promote grouping and facilitate positive FDS for yellow males, mediating the movement of yellow plumage across this hybrid zone.
Influence of finite‐sites mutation, population subdivision and sampling schemes on patterns of nucleotide polymorphism for species with molecular hyperdiversity
Authors: CUTTER ASHER D. , WANG GUO‐XIU , AI HUI , PENG YUE 
Published: February 2012

AbstractMolecular hyperdiversity has been documented in viruses, prokaryotes and eukaryotes. Such organisms undermine the assumptions of the infinite‐sites mutational model, because multiple mutational events at a site comprise a non‐negligible portion of polymorphisms. Moreover, different sampling schemes of individuals from species with subdivided populations can profoundly influence resulting patterns and interpretations of molecular variation. Inspired by molecular hyperdiversity in the nematode Caenorhabditis sp. 5, which exhibits average pairwise differences among synonymous sites of >5% as well as modest population structure, we investigated via coalescent simulation the joint effects of a finite‐sites mutation (FSM) process and population subdivision on the variant frequency spectrum. From many demes interconnected through a stepping‐stone migration model, we constructed local samples from a single deme, pooled samples from several demes and scattered samples of a single individual from numerous demes. Compared with a single panmictic population at equilibrium, we find that high population mutation rates induce a deficit of rare variants (positive Tajima’s D) under a FSM model. Population structure also induces such a skew for local samples when migration is high and for pooled samples when migration is low. Contrasts of sampling schemes for C. sp. 5 imply high mutational input coupled with high migration. We propose that joint analysis of local, pooled and scattered samples for species with subdivided populations provides a means of improving inference of demographic history, by virtue of the partially distinct patterns of polymorphism that manifest when sequences are analyzed according to differing sampling schemes.
The EDLL motif: a potent plant transcriptional activation domain from AP2/ERF transcription factors
Authors: Tiwari Shiv B. , Belachew Alemu , Ma Siu Fong , Young Melinda , Ade Jules , Shen Yu , Marion Colleen M. , Holtan Hans E. , Bailey Adina , Stone Jeffrey K. , Edwards Leslie , Wallace Andreah D. , Canales Roger D. , Adam Luc , Ratcliffe Oliver J. , Repetti Peter P. 
Published: February 2012

SummaryIn plants, the ERF/EREBP family of transcriptional regulators plays a key role in adaptation to various biotic and abiotic stresses. These proteins contain a conserved AP2 DNA‐binding domain and several uncharacterized motifs. Here, we describe a short motif, termed ‘EDLL’, that is present in AtERF98/TDR1 and other clade members from the same AP2 sub‐family. We show that the EDLL motif, which has a unique arrangement of acidic amino acids and hydrophobic leucines, functions as a strong activation domain. The motif is transferable to other proteins, and is active at both proximal and distal positions of target promoters. As such, the EDLL motif is able to partly overcome the repression conferred by the AtHB2 transcription factor, which contains an ERF‐associated amphiphilic repression (EAR) motif. We further examined the activation potential of EDLL by analysis of the regulation of flowering time by NF‐Y (nuclear factor Y) proteins. Genetic evidence indicates that NF‐Y protein complexes potentiate the action of CONSTANS in regulation of flowering in Arabidopsis; we show that the transcriptional activation function of CONSTANS can be substituted by direct fusion of the EDLL activation motif to NF‐YB subunits. The EDLL motif represents a potent plant activation domain that can be used as a tool to confer transcriptional activation potential to heterologous DNA‐binding proteins.
Post renal transplantation Kaposi's sarcoma: a review of its epidemiology, pathogenesis, diagnosis, clinical aspects, and therapy
Authors: Hosseini‐Moghaddam S.M. , Soleimanirahbar A. , Mazzulli T. , Rotstein C. , Husain S. 
Published: February 2012

Abstract:BackgroundKaposi's sarcoma (KS) is a vascular malignancy primarily involving the skin. This neoplasm occurs commonly in acquired immunodeficiency syndrome (AIDS) and post solid organ transplantation. Human herpesvirus type 8 (HHV‐8) has been shown to play a causative role in AIDS‐associated KS and in post renal transplantation KS.MethodsBased on a MEDLINE search, we present a review of the current information on the epidemiology, pathogenesis, diagnosis and treatment of post‐transplantation KS (PT‐KS) with an emphasis on renal transplantation.ResultThe different frequencies of PT‐KS in different parts of the world seem to be related to seroprevalence of HHV‐8 infection. Following renal transplantation and the administration of immunosuppressive therapy, HHV‐8 may reactivate. The renal tubular epithelium is a site for HHV‐8 latency. Rates of PT‐KS in seropositive recipients and anti‐HHV‐8 mismatched recipients (donor+/recipient−) are approximately 13% and 4.6%, respectively. Additional risk factors for the development of PT‐KS include skin color, country of birth, age at the time of transplantation, and different induction regimens including anti‐thymocyte globulin, steroid, or anti‐interleukin 2‐receptor antagonists. Skin is the major site of involvement. Surprisingly, involvement of the transplanted organ has been reported to be extremely rare. Reduction in immunosuppressive therapy and switching to mammalian targets of rapamycin inhibitors, such as sirolimus, are effective treatments for PT‐KS. In patients with no response to reduction in immunosuppressive therapy, systemic chemotherapy with different regimens has been reported to be successful.ConclusionPT‐KS in renal transplant patients is an important problem specifically in southern Europe and the Middle East. In the majority of patients, the diagnosis based on clinical suspicion is always essential. Clinicians should bear in mind that PT‐KS may threaten graft function and hence result in rejection complications. Appropriate management increases patient survival.
Sex‐biased genetic component distribution among populations: additive genetic and maternal contributions to phenotypic differences among populations of Chinook salmon
Authors: AYKANAT T. , BRYDEN C. A. , HEATH D. D. 
Published: February 2012

AbstractAn approach frequently used to demonstrate a genetic basis for population‐level phenotypic differences is to employ common garden rearing designs, where observed differences are assumed to be attributable to primarily additive genetic effects. Here, in two common garden experiments, we employed factorial breeding designs between wild and domestic, and among wild populations of Chinook salmon (Oncorhynchus tshawytscha). We measured the contribution of additive (VA) and maternal (VM) effects to the observed population differences for 17 life history and fitness‐related traits. Our results show that, in general, maternal effects contribute more to phenotypic differences among populations than additive genetic effects. These results suggest that maternal effects are important in population phenotypic differentiation and also signify that the inclusion of the maternal source of variation is critical when employing models to test population differences in salmon, such as in local adaptation studies.
Assortative mating for relatedness in a large naturally occurring population of Drosophila melanogaster
Authors: ROBINSON S. P. , KENNINGTON W. J. , SIMMONS L. W. 
Published: February 2012

AbstractNew theoretical work on kin selection and inclusive fitness benefits predicts that individuals will sometimes choose close or intermediate relatives as mates to maximize their fitness. However, empirical examples supporting such predictions are rare. In this study, we look for such evidence in a natural population of Drosophila melanogaster. We compared mating and nonmating individuals to test whether mating was nonrandom with respect to relatedness. Consistent with optimal inbreeding, males were more closely related to their mate than to randomly sampled females. However, all individuals collected mating showed higher relatedness and males were not significantly more related to their mate than to other mating females. We also found a negative relationship between relatedness and fecundity. Our results are consistent with the hypothesis that inclusive fitness benefits may drive inbreeding tolerance despite direct costs to fitness; however, an experimental approach is needed to investigate the link between mate preference and relatedness.
Plastic responses to parents and predators lead to divergent shoaling behaviour in sticklebacks
Authors: KOZAK G. M. , BOUGHMAN J. W. 
Published: February 2012

AbstractPopulation divergence in antipredator defence and behaviour occurs rapidly and repeatedly. Genetic differences, phenotypic plasticity or parental effects may all contribute to divergence, but the relative importance of each of these mechanisms remains unknown. We exposed juveniles to parents and predators to measure how induced changes contribute to shoaling behaviour differences between two threespine stickleback species (benthics and limnetics:Gasterosteusspp). We found that limnetics increased shoaling in response to predator attacks, whereas benthics did not alter their behaviour. Care by limnetic fathers led to increased shoaling in both limnetic and benthic offspring. Shoaling helps limnetics avoid trout and avian predation; our results suggest that this adaptive behaviour is the result of a combination of paternal effects, predator‐induced plasticity and genetic differences between species. These results suggest that plasticity substantially contributes to the rapid divergence in shoaling behaviour across the post‐Pleistocene radiation of sticklebacks.
Optimal body fat percentage cut‐offs for obesity in Chinese adults
Authors: Li Ling , Wang Chen , Bao Yuqian , Peng Liangpu , Gu Huilin , Jia Weiping 
Published: February 2012

Summary

Obesity results in an increased risk of metabolic syndrome (MetS) and Type 2 diabetes (T2DM). Body fat percentage (BF%) is a common index of body composition. The aim of the present study was to determine the optimal BF% cut‐offs for obesity to predict MetS and T2DM in Chinese adults.
The baseline study group comprised 3916 Chinese adults (age 30–70 years of age); 2033 subjects without MetS or T2DM were followed up for a maximum of 5.5 years. The BF% was estimated using bioelectrical impedance analysis. Optimal BF% cut‐offs were analysed by receiver operating characteristic (ROC) curves. Binary logistic regression analysis was performed to measure the association between obesity at baseline defined by BF% and newly developed MetS and T2DM.
Mean BF% levels were lower in men than in women (23.9 ± 6.1% vs 33.5 ± 7.1%, respectively; P < 0.01). For men, the optimal BF% cut‐offs for the prediction of MetS and T2DM were 25.45% and 26.65%, respectively; for women, the corresponding values were 34.95% and 36.55%. Subjects with high BF% (≥ 25% in men; ≥ 35% in women) had higher risks of incident MetS or T2DM than those with low BF% (< 25% in men; < 35% in women). The relative risks were 3.43 (95% confidence intervals (CI) 2.59–4.54) and 2.92 (95% CI 1.85–4.60), respectively.
The optimal BF% cut‐offs for obesity for the prediction of MetS and T2DM in Chinese men and women were around 25% and 35%, respectively.
Dangerous liaisons: Pancreatic stellate cells and pancreatic cancer cells
Authors: Apte Minoti V , Wilson Jeremy S 
Published: February 2012

AbstractOne of the characteristic features of the majority of pancreatic ductal adenocarcinomas is an abundant desmoplastic/stromal reaction. Until recently, this stroma had received little attention from researchers studying the pathogenesis of pancreatic cancer, with most of the research focus resting on the biology of tumor cells themselves. However, evidence is now accumulating that the stroma plays a critical role in pancreatic cancer progression. The cells responsible for producing the stromal reaction in pancreatic cancer are activated pancreatic stellate cells (PSCs, the key effector cells in pancreatic fibrogenesis). In vitro and in vivo studies have convincingly demonstrated a close bi‐directional interaction between PSCs and pancreatic cancer cells, which facilitates local tumor growth as well as distant metastasis. PSCs also interact closely with endothelial cells to stimulate angiogenesis and are possibly involved in the known resistance of pancreatic cancer to chemotherapy and radiation. Most interestingly, it has recently been shown that PSCs from the primary tumor can travel to distant metastatic sites where they likely facilitate the seeding, survival, and proliferation of cancer cells. Thus, it is now recognized that the stroma is an important alternative therapeutic target in this disease and concerted pre‐clinical research is underway to develop strategies to modulate/deplete the stromal reaction to inhibit cancer progression. The challenge is to translate these developments into clinically applicable treatments for patients.
Hepatoprotective and anti‐inflammatory cytokines in alcoholic liver disease
Authors: Gao Bin 
Published: February 2012

AbstractThe activation of innate immunity by various factors (e.g. lipopolysaccharide and complements) plays an important role in initiating and promoting alcoholic liver injury via the stimulation of Kupffer cells to induce oxidative stress and to produce pro‐inflammatory cytokines (e.g. tumor necrosis factor [TNF]‐α) that cause hepatocellular damage. Accumulating evidence suggests that the activation of innate immunity also stimulates Kupffer cells to produce the hepatoprotective cytokine interleukin‐6 (IL‐6) and the anti‐inflammatory cytokine IL‐10 during alcoholic liver injury. IL‐6 protects against alcoholic liver injury via the activation of signal transducer and activator of transcription 3 (STAT3) and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. IL‐10 inhibits alcoholic liver inflammation via the activation of STAT3 in Kupffer cells/macrophages and the subsequent inhibition of liver inflammation. Recent studies have suggested that IL‐10 may play a dual role in controlling ethanol‐induced steatosis and liver injury via the inhibition of the pro‐inflammatory cytokine TNF‐α, thereby ameliorating alcoholic liver injury, or via the inhibition of the hepatoprotective cytokine IL‐6, thereby potentiating alcoholic liver injury. IL‐22 is another important hepatoprotective cytokine that protects against acute and chronic alcoholic liver injury by binding to a receptor complex composed of IL‐10R2 and IL‐22R chains on the surfaces of hepatocytes. Finally, IL‐22 treatment is a potential therapeutic option for treating severe forms of alcoholic liver disease because of its antioxidant, antiapoptotic, antisteatotic, proliferative, and antimicrobial effects, as well as the potential added benefit of few side effects.
Impaired autophagy and organellar dysfunction in pancreatitis
Authors: Gukovsky Ilya , Pandol Stephen J , Mareninova Olga A , Shalbueva Natalia , Jia Wenzhuo , Gukovskaya Anna S 
Published: February 2012

AbstractRecent findings from our group, obtained on experimental in vivo and ex vivo models of pancreatitis, reveal that this disease causes a profound dysfunction of key cellular organelles, lysosomes and mitochondria. We found that autophagy, the main cellular degradative, lysosome‐driven process, is activated but also impaired in acute pancreatitis because of its' inefficient progression/resolution (flux) resulting from defective function of lysosomes. One mechanism underlying the lysosomal dysfunction in pancreatitis is abnormal processing (maturation) and activation of cathepsins, major lysosomal hydrolases; another is a decrease in pancreatic levels of key lysosomal membrane proteins LAMP‐1 and LAMP‐2. Our data indicate that lysosomal dysfunction plays an important initiating role in pancreatitis pathobiology. The impaired autophagy mediates vacuole accumulation in acinar cells; furthermore, the abnormal maturation and activation of cathepsins leads to increase in intra‐acinar trypsin, the hallmark of pancreatitis; and LAMP‐2 deficiency causes inflammation and acinar cell necrosis. Thus, the autophagic and lysosomal dysfunctions mediate key pathologic responses of pancreatitis. On the other hand, we showed that pancreatitis causes acinar cell mitochondria depolarization, mediated by the permeability transition pore (PTP). Genetic (via deletion of cyclophilin D) inactivation of PTP prevents mitochondrial depolarization and greatly ameliorates the pathologic responses of pancreatitis. Further, our data suggest that mitochondrial damage, by stimulating autophagy, increases the demand for efficient lysosomal degradation and therefore aggravates the pathologic consequences of lysosomal dysfunction. Thus, the combined autophagic, lysosomal and mitochondrial dysfunctions are key to the pathogenesis of pancreatitis.
Granulocytapheresis and plasma exchange for severe alcoholic hepatitis
Authors: Horie Yoshinori 
Published: February 2012

AbstractBackground and Aim:  Severe alcoholic hepatitis (SAH) is an inflammatory response with multiple morbidity factors like leucocytosis, hepatomegaly, renal failure, hepatic encephalopathy, endotoxemia, and a high mortality rate. Identifying therapeutic interventions that can improve prognosis is the goal of research.Methods:  Questionnaires were sent to 1234 medical institutions asking for information on patients with SAH during 2004 to 2008, including patients' demography, disease profile and the therapeutic interventions patients had received during hospitalization.Results:  Forty‐five hospitals had treated SAH patients, and provided full demographic data on 98 patients. Forty‐eight patients had received no treatment, 12 patients had received granulocytes/monocytes apheresis (GMA) to deplete elevated myeloid lineage leucocytes, the rest had received one or more of the following treatments, corticosteroids, plasma exchange (PE) and hemodialysis (HD). Further, 38 patients had died and 60 had survived within 100 days of hospitalization. Serum creatinine (Cr) was higher in patients who had died versus patients who had survived (P = 0.001). Likewise, patients with white blood cells (WBC) ≥ 104/µL had higher mortality rate versus patients with WBC < 104/µL (P = 0.018). GMA in patients with WBC ≥ 104/µL showed improved prognosis versus in patients with WBC ≥ 104/µL who did not receive GMA (P = 0.0006). Corticosteroids, plasma exchange and HD did not significantly impact prognosis of SAH patients.Conclusions:  Our perception is that, patients with elevated myeloid leucocytes benefit most from GMA, while plasma exchange appears to support patients with coagulation deficiency or high plasma bilirubin and HD has indication in patients with high Cr.