Correction: A multi-proxy assessment of the impact of environmental instability on Late Holocene (4500-3800 BP) Native American villages of the Georgia coast.

[This corrects the article DOI: 10.1371/journal.pone.

A 7000-year record of floods and ecological feedbacks in Weeks Bay, Alabama, USA.

Climate change, sea-level rise, and human activities present major concerns for coastal environments. Paleoenvironmental records allow us to extend the instrumented record and study recent environmental impacts in a long-term context with natural pre-industrial conditions. Here, we investigate grain size, stable carbon (δC) and nitrogen (δN) isotopes, elemental composition, and diatom abundance in sediments to construct a 7000-year paleoenvironmental history of Weeks Bay, Alabama, a NOAA National Estuarine Research Reserve.

Archaeological climate proxies and the complexities of reconstructing Holocene El Niño in coastal Peru.

Archaeological evidence plays a key role in longitudinal studies of humans and climate. Climate proxy data from Peruvian archaeological sites provide a case study through insight into the history of the "flavors" or varieties of El Niño (EN) events after ∼11 ka: eastern Pacific EN, La Niña, coastal EN (COA), and central Pacific or Modoki EN (CP). Archaeological proxies are important to the coastal Peruvian case because more commonly used paleoclimate proxies are unavailable or equivocal.

DNA methylation dynamics during embryonic development and postnatal maturation of the mouse auditory sensory epithelium.

The inner ear is a complex structure responsible for hearing and balance, and organ pathology is associated with deafness and balance disorders. To evaluate the role of epigenomic dynamics, we performed whole genome bisulfite sequencing at key time points during the development and maturation of the mouse inner ear sensory epithelium (SE). Our single-nucleotide resolution maps revealed variations in both general characteristics and dynamics of DNA methylation over time.

Methylome Analysis of Human Bone Marrow MSCs Reveals Extensive Age- and Culture-Induced Changes at Distal Regulatory Elements.

Human bone marrow stromal cells, or mesenchymal stem cells (BM-MSCs), need expansion prior to use as cell-based therapies in immunological and tissue repair applications. Aging and expansion of BM-MSCs induce epigenetic changes that can impact therapeutic outcomes. By applying sequencing-based methods, we reveal that the breadth of DNA methylation dynamics associated with aging and expansion is greater than previously reported.

Epigenomic Landscapes of hESC-Derived Neural Rosettes: Modeling Neural Tube Formation and Diseases.

We currently lack a comprehensive understanding of the mechanisms underlying neural tube formation and their contributions to neural tube defects (NTDs). Developing a model to study such a complex morphogenetic process, especially one that models human-specific aspects, is critical. Three-dimensional, human embryonic stem cell (hESC)-derived neural rosettes (NRs) provide a powerful resource for in vitro modeling of human neural tube formation.

Corrigendum: Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy.

This corrects the article DOI: 10.1038/ncomms14454.

An Activating STAT3 Mutation Causes Neonatal Diabetes through Premature Induction of Pancreatic Differentiation.

Activating germline mutations in STAT3 were recently identified as a cause of neonatal diabetes mellitus associated with beta-cell autoimmunity. We have investigated the effect of an activating mutation, STAT3, on pancreatic development using induced pluripotent stem cells (iPSCs) derived from a patient with neonatal diabetes and pancreatic hypoplasia. Early pancreatic endoderm differentiated similarly from STAT3 and healthy-control cells, but in later stages, NEUROG3 expression was upregulated prematurely in STAT3 cells together with insulin (INS) and glucagon (GCG).

δN Values in Crassostrea virginica Shells Provides Early Direct Evidence for Nitrogen Loading to Chesapeake Bay.

Crassostrea virginica is one of the most common estuarine bivalves in the United States' east coast and is frequently found in archaeological sites and sub-fossil deposits. Although there have been several sclerochronological studies on stable carbon and oxygen isotopes in the shells of this species, less is known about δN values within their shells, which could be a useful paleoenvironmental proxy to assess estuarine nitrogen dynamics. Modern C.

Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy.

Gene replacement therapies utilizing adeno-associated viral (AAV) vectors hold great promise for treating Duchenne muscular dystrophy (DMD). A related approach uses AAV vectors to edit specific regions of the DMD gene using CRISPR/Cas9. Here we develop multiple approaches for editing the mutation in dystrophic mdx mice using single and dual AAV vector delivery of a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, in one approach, a dystrophin homology region to fully correct the mutation.

Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential.

Reports on the retention of somatic cell memory in induced pluripotent stem cells (iPSCs) have complicated the selection of the optimal cell type for the generation of iPSC biobanks. To address this issue we compared transcriptomic, epigenetic, and differentiation propensities of genetically matched human iPSCs derived from fibroblasts and blood, two tissues of the most practical relevance for biobanking. Our results show that iPSC lines derived from the same donor are highly similar to each other.

cChIP-seq: a robust small-scale method for investigation of histone modifications.

Background: ChIP-seq is highly utilized for mapping histone modifications that are informative about gene regulation and genome annotations. For example, applying ChIP-seq to histone modifications such as H3K4me1 has facilitated generating epigenomic maps of putative enhancers. This powerful technology, however, is limited in its application by the large number of cells required.

Gastrointestinal torsions and intussusception in northern koalas (Phascolarctos cinereus) at San Diego Zoo (1976-2012).

The recent classification as threatened status of the northern koala (Phascolarctos cinereus) by the Australian Government highlights the importance of the conservation and health management of this iconic Australian marsupial. This case series describes gastrointestinal torsion and intussusception in six northern koalas (three males, three females, 2-11 yr old) at the San Diego Zoo from 1976 to 2012. Two koalas died shortly after presentation.

El Niño impact on mollusk biomineralization-implications for trace element proxy reconstructions and the paleo-archeological record.

Marine macroinvertebrates are ideal sentinel organisms to monitor rapid environmental changes associated with climatic phenomena. These organisms build up protective exoskeletons incrementally by biologically-controlled mineralization, which is deeply rooted in long-term evolutionary processes. Recent studies relating potential rapid environmental fluctuations to climate change, such as ocean acidification, suggest modifications on carbonate biominerals of marine invertebrates.

Evaluating the utility of an accelerometer and urinary hormone analysis as indicators of estrus in a Zoo-housed koala (Phascolarctos cinereus).

Induced ovulators, such as the koala, do not always have overt signs of estrus, which makes pairing these animals for breeding purposes difficult to achieve in a zoo setting. This study examined the possibility of using alternative methods to behavioral sampling and weight fluctuations for monitoring estrus in a female koala of reproductive age. We attempt to gain an improved understanding of koala estrus and enhance our ability to detect it by combining a noninvasive technique for hormone analysis with a newer method for recording activity level.

Risk factors for chronic pain following breast cancer surgery: a prospective study.

Unlabelled: Chronic pain following breast cancer surgery is associated with decreased health-related quality of life and is a source of additional psychosocial distress in women who are already confronting the multiple stresses of cancer. Few prospective studies have identified risk factors for chronic pain following breast cancer surgery. Putative demographic, clinical, and psychosocial risk factors for chronic pain were evaluated prospectively in 95 women scheduled for breast cancer surgery.

Directed postgraduate study result in quantitative improvement in American Board of Surgery In-Training Exam scores.

Background: The collective study habits of 1 group of residents involved in educationally distinct periods of time in a community-based general surgery residency program were evaluated.

Methods: American Board of Surgery In-Training Exam (ABSITE) score results of 31 residents were calculated during 3 distinctive educational time periods: resident independent, self-directed study; resident-directed study with weekly systematic textbook reviews; and faculty-directed study with additional formal basic science and clinical lectures.

Results: Aggregate higher scores were observed when ABSITE results for the directed study period were compared with those observed during the independent study period in mid-level resident years (postgraduate year [PGY] 2 to 4).

Risk factors for acute pain and its persistence following breast cancer surgery.

Although more severe acute postoperative pain increases the risk of chronic pain following breast cancer surgery, few studies have examined the characteristics of patients who develop greater acute pain. To identify risk factors for acute pain and its persistence one month following breast cancer surgery, a sample of 114 women scheduled for breast cancer surgery was assessed preoperatively for demographic, clinical, and emotional functioning variables that were hypothesized to be associated with acute pain severity. Clinically meaningful postoperative pain was assessed at follow-up interviews 2, 10, and 30 days after surgery.

Otolith delta 18O record of mid-Holocene sea surface temperatures in Peru.

Peruvian sea catfish (Galeichthys peruvianus) sagittal otoliths preserve a record of modern and mid-Holocene sea surface temperatures (SSTs). Oxygen isotope profiles in otoliths excavated from Ostra [6010 +/- 90 years before the present (yr B.P.

Faulty design resulting in temporary pacemaker failure.

A 77-year-old man became asystolic 3 days after aortic valve replacement and coronary artery bypass surgery. A dual-chamber temporary pacemaker generator was turned on but failed to discharge; instead, an obscure error message appeared on the liquid crystal display of the pacemaker. The intensive-care nurses and physicians were unable to activate the pacemaker.