bluuebunny/crossref_metadata_2025_split huggingface dataset:
The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage
Authors: Kumar Satish , Padmanabham PBSV , Ravuri Rajasekhara R , Uttaravalli Kiran , Koneru Padmaja , Mukherjee P Aditi , Das B , Kotal M , Xaviour D , Saheb SY , Rao VR 
Published: August 2008

Abstract

Background
The "out of Africa" model postulating single "southern route" dispersal posits arrival of "Anatomically Modern Human" to Indian subcontinent around 66–70 thousand years before present (kyBP). However the contributions and legacy of these earliest settlers in contemporary Indian populations, owing to the complex past population dynamics and later migrations has been an issue of controversy. The high frequency of mitochondrial lineage "M2" consistent with its greater age and distribution suggests that it may represent the phylogenetic signature of earliest settlers. Accordingly, we attempted to re-evaluate the impact and contribution of earliest settlers in shaping the genetic diversity and structure of contemporary Indian populations; using our newly sequenced 72 and 4 published complete mitochondrial genomes of this lineage.

Results
The M2 lineage, harbouring two deep rooting subclades M2a and M2b encompasses approximately one tenth of the mtDNA pool of studied tribes. The phylogeographic spread and diversity indices of M2 and its subclades among the tribes of different geographic regions and linguistic phyla were investigated in detail. Further the reconstructed demographic history of M2 lineage as a surrogate of earliest settlers' component revealed that the demographic events with pronounced regional variations had played pivotal role in shaping the complex net of populations phylogenetic relationship in Indian subcontinent.

Conclusion
Our results suggest that tribes of southern and eastern region along with Dravidian and Austro-Asiatic speakers of central India are the modern representatives of earliest settlers of subcontinent. The Last Glacial Maximum aridity and post LGM population growth mechanised some sort of homogeneity and redistribution of earliest settlers' component in India. The demic diffusion of agriculture and associated technologies around 3 kyBP, which might have marginalized hunter-gatherer, is coincidental with the decline of earliest settlers' population during this period.
Duplications and functional divergence of ADP-glucose pyrophosphorylase genes in plants
Authors: Georgelis Nikolaos , Braun Edward L , Hannah L Curtis 
Published: August 2008

Abstract

Background
ADP-glucose pyrophosphorylase (AGPase), which catalyses a rate limiting step in starch synthesis, is a heterotetramer comprised of two identical large and two identical small subunits in plants. Although the large and small subunits are equally sensitive to activity-altering amino acid changes when expressed in a bacterial system, the overall rate of non-synonymous evolution is ~2.7-fold greater for the large subunit than for the small subunit. Herein, we examine the basis for their different rates of evolution, the number of duplications in both large and small subunit genes and document changes in the patterns of AGPase evolution over time.

Results
We found that the first duplication in the AGPase large subunit family occurred early in the history of land plants, while the earliest small subunit duplication occurred after the divergence of monocots and eudicots. The large subunit also had a larger number of gene duplications than did the small subunit. The ancient duplications in the large subunit family raise concern about the saturation of synonymous substitutions, but estimates of the absolute rate of AGPase evolution were highly correlated with estimates of ω (the non-synonymous to synonymous rate ratio). Both subunits showed evidence for positive selection and relaxation of purifying selection after duplication, but these phenomena could not explain the different evolutionary rates of the two subunits. Instead, evolutionary constraints appear to be permanently relaxed for the large subunit relative to the small subunit. Both subunits exhibit branch-specific patterns of rate variation among sites.

Conclusion
These analyses indicate that the higher evolutionary rate of the plant AGPase large subunit reflects permanent relaxation of constraints relative to the small subunit and they show that the large subunit genes have undergone more gene duplications than small subunit genes. Candidate sites potentially responsible for functional divergence within each of the AGPase subunits were investigated by examining branch-specific patterns of rate variation. We discuss the phenotypes of mutants that alter some candidate sites and strategies for examining candidate sites of presently unknown function.
The genomic distribution of intraspecific and interspecific sequence divergence of human segmental duplications relative to human/chimpanzee chromosomal rearrangements
Authors: Marques-Bonet Tomàs , Cheng Ze , She Xinwei , Eichler Evan E , Navarro Arcadi 
Published: August 2008

Abstract

Background
It has been suggested that chromosomal rearrangements harbor the molecular footprint of the biological phenomena which they induce, in the form, for instance, of changes in the sequence divergence rates of linked genes. So far, all the studies of these potential associations have focused on the relationship between structural changes and the rates of evolution of single-copy DNA and have tried to exclude segmental duplications (SDs). This is paradoxical, since SDs are one of the primary forces driving the evolution of structure and function in our genomes and have been linked not only with novel genes acquiring new functions, but also with overall higher DNA sequence divergence and major chromosomal rearrangements.

Results
Here we take the opposite view and focus on SDs. We analyze several of the features of SDs, including the rates of intraspecific divergence between paralogous copies of human SDs and of interspecific divergence between human SDs and chimpanzee DNA. We study how divergence measures relate to chromosomal rearrangements, while considering other factors that affect evolutionary rates in single copy DNA.

Conclusion
We find that interspecific SD divergence behaves similarly to divergence of single-copy DNA. In contrast, old and recent paralogous copies of SDs do present different patterns of intraspecific divergence. Also, we show that some relatively recent SDs accumulate in regions that carry inversions in sister lineages.
Methylprednisolone inhibits interleukin-17 and interferon-gamma expression by both naive and primed T cells
Authors: Momčilović Miljana , Miljković Željka , Popadić Dušan , Marković Miloš , Savić Emina , Ramić Zorica , Miljković Djordje , Mostarica-Stojković Marija 
Published: August 2008

AbstractBackgroundInterleukin-17 (IL-17)-producing cells are increasingly considered to be the major pathogenic population in various autoimmune disorders. The effects of glucocorticoids, widely used as therapeutics for inflammatory and autoimmune disorders, on IL-17 generation have not been thoroughly investigated so far. Therefore, we have explored the influence of methylprednisolone (MP) on IL-17 expression in rat lymphocytes, and compared it to the effect of the drug on interferon (IFN)-γ.ResultsProduction of IL-17 in mitogen-stimulated lymph node cells (LNC) from non-treated rats, as well as in myelin basic protein (MBP)-stimulated draining LNC from rats immunized with spinal cord homogenate and complete Freund's adjuvant was significantly reduced by MP. The reduction was dose-dependent, sustained through the follow-up period of 48 hours, and was not achieved through anti-proliferative effect. Additionally, MP inhibited IL-17 production in purified T cells as well, but to less extent than in LNC. In its influence on IL-17 production MP inhibited Ror-γT transcription factor expression, as well as Jun phosphorylation, but not ERK or p38 activation in mitogen-stimulated LNC. Importantly, MP collaborated with IFN-γ in inhibiting IL-17 generation in LNC.ConclusionThe observed difference in the effect of MP on IL-17 and IFN-γ could be important for the understanding of the variability in the efficiency of glucocorticoids in the treatment of autoimmune diseases.
Roles of PI3K and JAK pathways in viability of retinal ganglion cells after acute elevation of intraocular pressure in rats with different autoimmune backgrounds
Authors: Huang Yao , Li Zhiwei , Wang Ningli , van Rooijen Nico , Cui Qi 
Published: August 2008

Abstract

Background
We recently showed that whereas inhibition of PI3K/akt or JAK/STAT pathway promoted retinal ganglion cell (RGC) survival after optic nerve (ON) injury in Fischer 344 (F344) rats, the same inhibition resulted in aggravated RGC loss after acute intraocular pressure (IOP) elevation in Sprague Dawley (SPD) rats. In addition, the responses of macrophages to ON injury and acute IOP elevation were different between F344 and Lewis rats, i.e., different autoimmune profiles. Using an acute IOP elevation paradigm in this study, we investigated 1) whether autoimmune background influences PI3K/akt and JAK/STAT functions by examining the effect of PI3K/akt and JAK/STAT pathway inhibition on RGC survival in F344 and Lewis rats, and 2) whether differential actions of macrophages occur in PI3K/akt and JAK/STAT pathways-dependent modulation of RGC survival. IOP elevation was performed at 110 mmHg for 2 hours. PI3K/akt and JAK/STAT pathway inhibitors were applied intravitreally to block their respective pathway signaling transduction. Because macrophage invasion was seen in the eye after the pathway inhibition, to examine the role of these pathways independent of macrophages, macrophages in the retina were removed by intravitreal application of clodronate liposomes. Viable RGCs were retrogradely labelled by FluoroGold 40 hours before animal sacrifice.

Results
Similar to what was previously observed, significantly more RGCs were lost in Lewis than F344 rats 3 weeks after acute IOP elevation. As in SPD rats, inhibition of the PI3K/akt or JAK/STAT pathway increased the loss of RGCs in both F344 and Lewis rats. Removal of macrophages in the eye by clodronate liposomes reduced RGC loss due to pathway inhibition in both strains.

Conclusion
This study demonstrates that following acute IOP elevation 1) PI3K/akt and JAK/STAT pathways mediate RGC survival in both F344 and Lewis rats, 2) autoimmune responses do not influence the functions of these two pathways, and 3) PI3K/akt and JAK/STAT pathway inhibition-dependent activation of macrophages is detrimental to RGCs.
Visuo-auditory interactions in the primary visual cortex of the behaving monkey: Electrophysiological evidence
Authors: Wang Ye , Celebrini Simona , Trotter Yves , Barone Pascal 
Published: August 2008

AbstractBackgroundVisual, tactile and auditory information is processed from the periphery to the cortical level through separate channels that target primary sensory cortices, from which it is further distributed to functionally specialized areas. Multisensory integration is classically assigned to higher hierarchical cortical areas, but there is growing electrophysiological evidence in man and monkey of multimodal interactions in areas thought to be unimodal, interactions that can occur at very short latencies. Such fast timing of multisensory interactions rules out the possibility of an origin in the polymodal areas mediated through back projections, but is rather in favor of heteromodal connections such as the direct projections observed in the monkey, from auditory areas (including the primary auditory cortex AI) directly to the primary visual cortex V1. Based on the existence of such AI to V1 projections, we looked for modulation of neuronal visual responses in V1 by an auditory stimulus in the awake behaving monkey.ResultsBehavioral or electrophysiological data were obtained from two behaving monkeys. One monkey was trained to maintain a passive central fixation while a peripheral visual (V) or visuo-auditory (AV) stimulus was presented. From a population of 45 V1 neurons, there was no difference in the mean latencies or strength of visual responses when comparing V and AV conditions. In a second active task, the monkey was required to orient his gaze toward the visual or visuo-auditory stimulus. From a population of 49 cells recorded during this saccadic task, we observed a significant reduction in response latencies in the visuo-auditory condition compared to the visual condition (mean 61.0 vs. 64.5 ms) only when the visual stimulus was at midlevel contrast. No effect was observed at high contrast.ConclusionOur data show that single neurons from a primary sensory cortex such as V1 can integrate sensory information of a different modality, a result that argues against a strict hierarchical model of multisensory integration. Multisensory interaction in V1 is, in our experiment, expressed by a significant reduction in visual response latencies specifically in suboptimal conditions and depending on the task demand. This suggests that neuronal mechanisms of multisensory integration are specific and adapted to the perceptual features of behavior.
In vitro tooth whitening effect of two medicated chewing gums compared to a whitening gum and saliva
Authors: Moore Michael , Hasler-Nguyen Nathalie , Saroea Geoffrey 
Published: August 2008

AbstractBackgroundExtrinsic staining of teeth may result from the deposition of a variety of pigments into or onto the tooth surface, which originate mainly from diet or from tobacco use. More recently, clinical studies have demonstrated the efficacy of some chewing gums in removing extrinsic tooth staining. The aim of this study was to assess the effectiveness of two nicotine medicated chewing gums (A and B) on stain removal in anin vitroexperiment, when compared with a confectionary whitening chewing gum (C) and human saliva (D).MethodsBovine incisors were stained by alternating air exposure and immersion in a broth containing natural pigments such as coffee, tea and oral microorganisms for 10 days. Stained enamel samples were exposed to saliva alone or to the test chewing gums under conditions simulating human mastication. The coloration change of the enamel samples was measured using a spectrophotometer. Measurements were obtained for each specimen (average of three absorbances) using the L*a*b scale: lightness (L*), red-green (a) and yellow-blue (b).ResultsMedicated chewing gums (A and B) removed a greater amount of visible extrinsic stain, while the confectionary chewing gum with a whitening claim (C) had a milder whitening effect as evaluated by quantitative and qualitative assessment.ConclusionThe tested Nicotine Replacement Therapy (NRT) chewing gums were more effective in the removal of the extrinsic tooth stain. This visible improvement in tooth whitening appearance could strengthen the smokers' motivation to quit smoking.
Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal rat
Authors: Leonardo Christopher C , Eakin Autumn K , Ajmo Joanne M , Collier Lisa A , Pennypacker Keith R , Strongin Alex Y , Gottschall Paul E 
Published: August 2008

AbstractBackgroundHypoxia-ischemia (H-I) can produce widespread neurodegeneration and deep cerebral white matter injury in the neonate. Resident microglia and invading leukocytes promote lesion progression by releasing reactive oxygen species, proteases and other pro-inflammatory mediators. After injury, expression of the gelatin-degrading matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are thought to result in the proteolysis of extracellular matrix (ECM), activation of cytokines/chemokines, and the loss of vascular integrity. Thus, therapies targeting ECM degradation and progressive neuroinflammation may be beneficial in reducing H-I – induced neuropathy. Minocycline has MMP-inhibitory properties and is both anti-inflammatory and neuroprotective. AG3340 (prinomastat) is an MMP inhibitor with high selectivity for the gelatinases. The purpose of this study was to determine whether these compounds could limit H-I – induced injury when administered at a delayed time point.MethodsSprague-Dawley rats were exposed to H-I at postnatal day 7 (P7), consisting of unilateral carotid artery ligation followed by 90 min exposure to 8% O2. Minocycline, AG3340, or vehicle were administered once daily for 6 days, beginning 24 hours after insult. Animals were sacrificed at P14 for neurohistological assessments. Immunohistochemistry was performed to determine the degree of reactive astrogliosis and immune cell activation/recruitment. Neural injury was detected using the Fluoro-Jade stain, a marker that identifies degenerating cells.ResultsCD11b and glial fibrillary acidic protein (GFAP) immunopositive cells increased in ipsilateral cortex after treatment with vehicle alone, demonstrating microglia/macrophage recruitment and reactive astrogliosis, respectively. Fluoro-Jade staining was markedly increased throughout the fronto-parietal cortex, striatum and hippocampus. Treatment with minocycline or AG3340 inhibited microglia/macrophage recruitment, attenuated astrogliosis and reduced Fluoro-Jade staining when compared to vehicle alone.ConclusionThe selective gelatinase inhibitor AG3340 showed equal efficacy in reducing neural injury and dampening neuroinflammation when compared to the anti-inflammatory compound minocycline. Thus, MMP-2 and MMP-9 may be viable therapeutic targets to treat neonatal brain injury.
Ethical challenges with the left ventricular assist device as a destination therapy
Authors: Rizzieri Aaron G , Verheijde Joseph L , Rady Mohamed Y , McGregor Joan L 
Published: August 2008

Abstract
The left ventricular assist device was originally designed to be surgically implanted as a bridge to transplantation for patients with chronic end-stage heart failure. On the basis of the REMATCH trial, the US Food and Drug Administration and the US Centers for Medicare & Medicaid Services approved permanent implantation of the left ventricular assist device as a destination therapy in Medicare beneficiaries who are not candidates for heart transplantation. The use of the left ventricular assist device as a destination therapy raises certain ethical challenges. Left ventricular assist devices can prolong the survival of average recipients compared with optimal medical management of chronic end-stage heart failure. However, the overall quality of life can be adversely affected in some recipients because of serious infections, neurologic complications, and device malfunction. Left ventricular assist devices alter end-of-life trajectories. The caregivers of recipients may experience significant burden (e.g., poor physical health, depression, anxiety, and posttraumatic stress disorder) from destination therapy with left ventricular assist devices. There are also social and financial ramifications for recipients and their families. We advocate early utilization of a palliative care approach and outline prerequisite conditions so that consenting for the use of a left ventricular assist device as a destination therapy is a well informed process. These conditions include: (1) direct participation of a multidisciplinary care team, including palliative care specialists, (2) a concise plan of care for anticipated device-related complications, (3) careful surveillance and counseling for caregiver burden, (4) advance-care planning for anticipated end-of-life trajectories and timing of device deactivation, and (5) a plan to address the long-term financial burden on patients, families, and caregivers.
Short-term mechanical circulatory devices (e.g. percutaneous cardiopulmonary bypass, percutaneous ventricular assist devices, etc.) can be initiated in emergency situations as a bridge to permanent implantation of ventricular assist devices in chronic end-stage heart failure. In the absence of first-person (patient) consent, presumed consent or surrogate consent should be used cautiously for the initiation of short-term mechanical circulatory devices in emergency situations as a bridge to permanent implantation of left ventricular assist devices. Future clinical studies of destination therapy with left ventricular assist devices should include measures of recipients' quality of end-of-life care and caregivers' burden.
Constructing disease-specific gene networks using pair-wise relevance metric: Application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements
Authors: Jiang Wei , Li Xia , Rao Shaoqi , Wang Lihong , Du Lei , Li Chuanxing , Wu Chao , Wang Hongzhi , Wang Yadong , Yang Baofeng 
Published: August 2008

Abstract

Background
With the advance of large-scale omics technologies, it is now feasible to reversely engineer the underlying genetic networks that describe the complex interplays of molecular elements that lead to complex diseases. Current networking approaches are mainly focusing on building genetic networks at large without probing the interaction mechanisms specific to a physiological or disease condition. The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases.

Results
The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8) (p ≈ 0), desmin (DES) (p = 2.71 × 10-6) and enolase 1 (ENO1) (p = 4.19 × 10-5)], while two novel hub genes [RNA binding motif protein 9 (RBM9) (p = 1.50 × 10-4) and ribosomal protein L30 (RPL30) (p = 1.50 × 10-4)] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO) based analysis of the colon cancer-specific gene network and the sub-network that consisted of three-way gene interactions suggested that tumourigenesis in colon cancer resulted from dysfunction in protein biosynthesis and categories associated with ribonucleoprotein complex which are well supported by multiple lines of experimental evidence.

Conclusion
This study demonstrated that IL8, DES and ENO1 act as the central elements in colon cancer susceptibility, and protein biosynthesis and the ribosome-associated function categories largely account for the colon cancer tumuorigenesis. Thus, the newly developed relevancy-based networking approach offers a powerful means to reverse-engineer the disease-specific network, a promising tool for systematic dissection of complex diseases.