Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
4,644
result(s) for
"Richards, B."
Sort by:
The Expansion of mtDNA Haplogroup L3 within and out of Africa
Although fossil remains show that anatomically modern humans dispersed out of Africa into the Near East ∼100 to 130 ka, genetic evidence from extant populations has suggested that non-Africans descend primarily from a single successful later migration. Within the human mitochondrial DNA (mtDNA) tree, haplogroup L3 encompasses not only many sub-Saharan Africans but also all ancient non-African lineages, and its age therefore provides an upper bound for the dispersal out of Africa. An analysis of 369 complete African L3 sequences places this maximum at ∼70 ka, virtually ruling out a successful exit before 74 ka, the date of the Toba volcanic supereruption in Sumatra. The similarity of the age of L3 to its two non-African daughter haplogroups, M and N, suggests that the same process was likely responsible for both the L3 expansion in Eastern Africa and the dispersal of a small group of modern humans out of Africa to settle the rest of the world. The timing of the expansion of L3 suggests a link to improved climatic conditions after ∼70 ka in Eastern and Central Africa rather than to symbolically mediated behavior, which evidently arose considerably earlier. The L3 mtDNA pool within Africa suggests a migration from Eastern Africa to Central Africa ∼60 to 35 ka and major migrations in the immediate postglacial again linked to climate. The largest population size increase seen in the L3 data is 3–4 ka in Central Africa, corresponding to Bantu expansions, leading diverse L3 lineages to spread into Eastern and Southern Africa in the last 3–2 ka.
Journal Article
Regulating reproductive donation
This title brings together different disciplinary perspectives and new empirical insights to explore the regulation of assisted reproduction around the world.
Book
Genetic and archaeological perspectives on the initial modern human colonization of southern Asia
It has been argued recently that the initial dispersal of anatomically modern humans from Africa to southern Asia occurred before the volcanic “supereruption” of the Mount Toba volcano (Sumatra) at ∼74,000 y before present (B.P.)—possibly as early as 120,000 y B.P. We show here that this “pre-Toba” dispersal model is in serious conflict with both the most recent genetic evidence from both Africa and Asia and the archaeological evidence from South Asian sites. We present an alternative model based on a combination of genetic analyses and recent archaeological evidence from South Asia and Africa. These data support a coastally oriented dispersal of modern humans from eastern Africa to southern Asia ∼60–50 thousand years ago (ka). This was associated with distinctively African microlithic and “backed-segment” technologies analogous to the African “Howiesons Poort” and related technologies, together with a range of distinctively “modern” cultural and symbolic features (highly shaped bone tools, personal ornaments, abstract artistic motifs, microblade technology, etc.), similar to those that accompanied the replacement of “archaic” Neanderthal by anatomically modern human populations in other regions of western Eurasia at a broadly similar date.
Journal Article
Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component
A two-step process, in which circulating levels of amyloid P are reduced and then anti–serum amyloid P antibody is given to activate macrophage clearance mechanisms of tissue deposits, appears to reduce amyloid deposits in liver and some other organs.
In systemic amyloidosis, the extracellular deposition of normally soluble plasma proteins as insoluble amyloid fibrils damages the structure and function of tissues and organs.
1
Current treatment consists of support or replacement of failing organs and measures to reduce the abundance of the amyloid fibril precursor protein.
1
,
2
A sufficient reduction of precursor supply arrests the accumulation of amyloid and can reduce morbidity and mortality. However, amyloid regression is very slow and often does not occur at all, in contrast to the usually swift clearance of other extracellular debris and efficient tissue remodeling — for example, after trauma. At least 65% . . .
Journal Article
Evaluating topographic wetness indices across central New York agricultural landscapes
Accurately predicting soil moisture patterns in the landscape is a persistent challenge. In humid regions, topographic wetness indices (TWIs) are widely used to approximate relative soil moisture patterns. However, there are many ways to calculate TWIs and very few field studies have evaluated the different approaches – especially in the US. We calculated TWIs using over 400 unique formulations that considered different digital elevation model (DEM) resolutions (cell size), vertical precision of DEM, flow direction and slope algorithms, smoothing via low-pass filtering, and the inclusion of relevant soil properties. We correlated each TWI with observed patterns of soil moisture at five agricultural fields in central NY, USA, with each field visited five to eight times between August and November 2012. Using a mixed effects modeling approach, we were able to identify optimal TWI formulations applicable to moderate relief agricultural settings that may provide guidance for practitioners and future studies. Overall, TWIs were moderately well correlated with observed soil moisture patterns; in the best case the relationship between TWI and soil moisture had an average R2 and Spearman correlation value of 0.61 and 0.78, respectively. In all cases, fine-scale (3 m) lidar-derived DEMs worked better than USGS 10 m DEMs and, in general, including soil properties improved correlations.
Journal Article
A dispersal of Homo sapiens from southern to eastern Africa immediately preceded the out-of-Africa migration
Africa was the birth-place of
Homo sapiens
and has the earliest evidence for symbolic behaviour and complex technologies. The best-attested early flowering of these distinctive features was in a glacial refuge zone on the southern coast 100–70 ka, with fewer indications in eastern Africa until after 70 ka. Yet it was eastern Africa, not the south, that witnessed the first major demographic expansion, ~70–60 ka, which led to the peopling of the rest of the world. One possible explanation is that important cultural traits were transmitted from south to east at this time. Here we identify a mitochondrial signal of such a dispersal soon after ~70 ka – the only time in the last 200,000 years that humid climate conditions encompassed southern and tropical Africa. This dispersal immediately preceded the out-of-Africa expansions, potentially providing the trigger for these expansions by transmitting significant cultural elements from the southern African refuge.
Journal Article
Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression
Dysregulation of the alternative pathway (AP) of the complement system is a significant contributor to age-related macular degeneration (AMD), a primary cause of irreversible vision loss worldwide. Here, we assess the contribution of the liver-produced complement factor H-related 4 protein (FHR-4) to AMD initiation and course of progression. We show that FHR-4 variation in plasma and at the primary location of AMD-associated pathology, the retinal pigment epithelium/Bruch’s membrane/choroid interface, is entirely explained by three independent quantitative trait loci (QTL). Using two distinct cohorts composed of a combined 14,965 controls and 20,741 cases, we ascertain that independent QTLs for FHR-4 are distinct from variants causally associated with AMD, and that FHR-4 variation is not independently associated with disease. Additionally, FHR-4 does not appear to influence AMD progression course among patients with disease driven predominantly by AP dysregulation. Modulation of FHR-4 is therefore unlikely to be an effective therapeutic strategy for AMD.
C
omplement factor H-related 4 protein (FHR-4) has been implicated in the pathophysiology of age-related macular degeneration (AMD). Here, in contrast, the authors find that levels of FHR-4 in plasma or ocular tissue do not appear to influence susceptibility to AMD or its course of progression, questioning whether modulation of FHR-4 is likely to be an effective therapeutic strategy.
Journal Article
Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis
In two placebo-controlled phase 3 trials, secukinumab, an anti–interleukin-17A monoclonal antibody, was effective in patients with ankylosing spondylitis. Adverse events associated with secukinumab included infections and neutropenia.
Ankylosing spondylitis is a chronic, immune-mediated disease that is characterized by inflammation and new bone formation in the axial skeleton
1
,
2
and that often results in progressive, irreversible structural damage, disability, deterioration of functioning, and a reduced quality of life.
3
,
4
Therapy with nonsteroidal antiinflammatory drugs (NSAIDs) is often insufficient to control symptoms, and there is no evidence that conventional disease-modifying antirheumatic drugs (DMARDs) are efficacious in axial disease.
5
Anti–tumor necrosis factor (TNF) therapy is currently recommended for patients with persistent disease activity despite conventional treatment.
5
In some patients, however, such therapy fails to achieve adequate disease control or has . . .
Journal Article
Spinal radiographic progression over 2 years in ankylosing spondylitis patients treated with secukinumab: a historical cohort comparison
Objective
The aim of this study was to compare radiographic progression in patients with ankylosing spondylitis (AS) treated for up to 2 years with secukinumab (MEASURE 1) with a historical cohort of biologic-naïve patients treated with NSAIDs (ENRADAS).
Methods
Baseline and 2-year lateral cervical and lumbar spine radiographs were independently evaluated using mSASSS by two readers, who were blinded to the chronology and cohort of the radiographs. The primary endpoint was the proportion of patients with no radiographic progression (mSASSS change ≤ 0 from baseline to year 2). The Primary Analysis Set included patients with baseline (≤ day 30) and post-baseline day 31–743 radiographs. Sensitivity analyses were performed to assess the robustness of the comparison between the two cohorts, as follows: Sensitivity Analysis Set 1 included all patients with baseline (≤ day 30) and year 2 (days 640–819) radiographs; Sensitivity Analysis Set 2 included all patients with baseline and post-baseline (> day 30) radiographs.
Results
A total of 168 patients (84%) from the MEASURE 1 cohort and 69 (57%) from the ENRADAS cohort qualified for the Primary Analysis Set. Over 2 years, the LS (SE) mean change from baseline in mSASSS for the primary analysis was 0.55 (0.139) for MEASURE 1 vs 0.89 (0.216) for ENRADAS (
p
= 0.1852). Mean changes from baseline in mSASSS were lower in MEASURE 1 vs ENRADAS for the primary and sensitivity analyses. The proportion of patients with no radiographic progression was consistently higher in the MEASURE 1 vs ENRADAS cohort across all cutoffs for no radiographic progression (change in mSASSS from baseline to year 2 of ≤ 0, ≤ 0.5, ≤ 1, and ≤ 2), but the differences were not statistically significant.
Conclusion
Secukinumab-treated patients demonstrated a numerical, but statistically non-significant, higher proportion of non-progressors and lower change in mSASSS over 2 years versus a cohort of biologic-naïve patients treated with NSAIDs.
Journal Article