This interpretation is supported by models of ocean currents arou

This interpretation is supported by models of ocean currents around Antarctica and PLX4032 implies an unrestricted oceanic connection across Antarctica between southern South America and the Tasman Sea. (C) 2011 Elsevier B.V. All rights reserved.”
“The colourful appearance of bird eggshells has long fascinated biologists and considerable research effort has focused on the structure and biochemistry of the avian eggshell matrix. The presence of tetrapyrrole

pigments was identified nearly a century ago. Surprisingly, how the concentrations of avian eggshell pigments vary among related species, and whether this variability is associated with either eggshell appearance and/or species life-history traits, remains poorly understood. We quantified the concentrations of the two key eggshell pigments, protoporphyrin IX and biliverdin, from a diverse sample of eggshells stored at the Natural History Museum, Tring, UK. We explicitly tested how these two pigments are associated with physical measures of eggshell coloration and whether

the pigment concentrations and colour diversity co-vary with phylogenetic affiliations among species. We also tested a series of comparative hypotheses regarding the association between the concentrations of the two pigments and specific life-history and breeding ecology traits. Across species, the average concentrations of protoporphyrin and biliverdin were positively correlated, and both strongly co-varied with phylogenetic relatedness. Controlling for phylogeny, protoporphyrin concentration was associated with a higher likelihood of cavity nesting and ground nesting, whereas biliverdin concentration was associated with LY2835219 a higher likelihood of non-cavity nesting habit and bi-parental provisioning. Selleck Liproxstatin-1 Although unlikely to be explained by a single function, the breeding ecology and life history-dependence of eggshell pigment concentrations in these comparative analyses implies that related species share pigment strategies, and that those strategies relate to broad adaptive roles in the evolution of variation in avian eggshell coloration and its underlying

mechanisms. (C) 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 106, 657672.”
“Background: Because early administration of intravenous fat emulsions (IVFEs) has been linked to infectious complications in trauma patients, we began withholding IVFE for the first seven to ten days of parenteral nutrition (PN) in all surgical intensive care unit (SICU) patients. Prior to this, IVFE had been infused from the start of PN.\n\nPurpose: To evaluate the influence of delaying IVFE on infectious complications in SICU patients.\n\nMethods: Retrospective review from October 2006 to June 2009 of SICU patients before and after a change in IVFE practice patterns in a 44-bed SICU at an academic medical center. Adult patients who received PN for more than six days were included.

We describe the characterization of a RA-activatable Cre transgen

We describe the characterization of a RA-activatable Cre transgene, which through crosses with a conditional reporter strain (the ROSA26R lacZ reporter), leads to a stable labeling of the cell populations experiencing RA signaling during embryogenesis. RA response-element (RARE) -driven Cre activity mimics at early stages the known activity of the corresponding RARE-lacZ transgene (Rossant et al., 1991). Stable labeling of the Cre-excised cell populations allows to trace the distribution of the RA-activated cell lineages at later stages. These are described in

relationship with current models of RA activity in various developmental systems, including the embryonic caudal region, limb buds, hindbrain, sensory organs, and heart. Developmental Dynamics 239:3260-3274, 2010. (C) 2010 Wiley-Liss, Inc.”
“Significant interest exists in strategies for improving forelimb function following spinal cord injury. We investigated the effect of enriched housing combined learn more with skilled training on the recovery of skilled and automatic forelimb function after a cervical spinal cord injury in adult rats. All animals were pretrained in skilled reaching, gridwalk crossing, and overground locomotion. Some received a cervical over-hemisection lesion at C4-5, interrupting the right side of the spinal cord and dorsal columns bilaterally, and were housed in standard Crenolanib price housing alone or enriched environments with daily training. A subset of animals received

rolipram to promote neuronal plasticity. Animals were tested weekly for 4 weeks to measure reaching, errors on the gridwalk, locomotion, and vertical exploration. Biotinylated dextran amine was injected into the cortex to label the corticospinal tract. Enriched environments/daily training significantly increased the number and success of left reaches compared to standard housing. Animals also made fewer errors on the gridwalk, a measure of coordinated forelimb function. However, there were no significant

improvements in forelimb use during vertical exploration or locomotion. Likewise, rolipram did not improve any of the behaviors tested. Both enriched housing and rolipram increased plasticity of the corticospinal tract rostral to the lesion. These studies indicate that skilled GSK2118436 training after a cervical spinal cord injury improves recovery of skilled forelimb use (reaching) and coordinated limb function (gridwalk) but does not improve automatic forelimb function (locomotion and vertical exploration). These studies suggest that rehabilitating forelimb function after spinal cord injury will require separate strategies for descending and segmental pathways.”
“SSL introduces ergonomic challenges while establishing the critical view during dissection of the Triangle of Calot (TOC). This study investigates the use of a novel percutaneous instrument platform and MAGS in performing SSL cholecystectomy with a technique that closely mimics four-port cholecystectomy.

Although most of these glycoproteins are produced in mammalian ce

Although most of these glycoproteins are produced in mammalian cells, there is concern that their large-scale production could be affected by an inadequate supply of bovine GSK621 price serum. There is also the risk of

viral infection spreading through the use of contaminated protein therapeutics. Consequently, protein expression systems in yeast have been established because protein manufacturing costs are cheaper than in mammalian cells, and yeast systems are virus-free. However, yeasts cannot generate human-type glycans, and thus cannot produce therapeutic glycoproteins for human use. There has therefore been considerable interest in glycan remodeling, from yeast-type to human-type. ‘Humanized’ glycoproteins can now be generated in yeast by disrupting yeast-specific glycosyltransferases and introducing genes responsible for sugar-nucleotide synthesis, its transported from the cytosol to Golgi lumen, as well as their transfer and hydrolysis. A compound that inhibits yeast O-mannosyltransferase

suppresses yeast-specific O-mannosyl modification, and can produce mucin-type glycoproteins. These systems are just being developed to the stage where the production in glycoengineered yeast of biopharmaceutical glycoproteins such as cytokines, antibodies for therapeutics, and enzymes for replacement therapy for lysosomal diseases are being evaluated for clinical applications. Yeast glycoprotein expression systems are expected to become the dominant approach for the production of human glycoproteins in the near future.”
“Cis-regulatory networks (CRNs) play a central role in cellular decision making. Like every selleck inhibitor other biological system, CRNs undergo evolution, which shapes their properties C59 Stem Cells & Wnt inhibitor by a combination of adaptive and nonadaptive evolutionary forces. Teasing apart these forces is an important step toward functional analyses of the different components of CRNs, designing regulatory perturbation experiments, and constructing synthetic networks. Although tests of neutrality and selection based on molecular sequence data exist, no such tests are currently available based on CRNs. In this work, we present a unique genotype model of CRNs that is grounded in a

genomic context and demonstrate its use in identifying portions of the CRN with properties explainable by neutral evolutionary forces at the system, subsystem, and operon levels. We leverage our model against experimentally derived data from Escherichia coli. The results of this analysis show statistically significant and substantial neutral trends in properties previously identified as adaptive in origin-degree distribution, clustering coefficient, and motifs-within the E. coli CRN. Our model captures the tightly coupled genome-interactome of an organism and enables analyses of how evolutionary events acting at the genome level, such as mutation, and at the population level, such as genetic drift, give rise to neutral patterns that we can quantify in CRNs.

12 nS and 1 7 nm, respectively LaCl3- and memantidine (MEM)-indu

12 nS and 1.7 nm, respectively. LaCl3- and memantidine (MEM)-induced block of this current

was also examined. The IC50 value for LaCl3- and MEM-induced inhibition of I-MEP was 35 and 75 mu M, respectively. However, unlike LaCl3, MEM (300 mu M) did not exert any effect on voltage-gated Ca2+ current. In inside-out configuration, MEM applied to either external or internal surface of the excised patch did not suppress the activity of ATP-sensitive K+ channels expressed in GH(3) cells, although glibenclamide significantly suppressed channel activity. This study provides the first evidence to show that MEM, a non-competitive antagonist of N-methyl MEK inhibitor D-aspartate receptors, directly inhibits the amplitude of I-MEP in pituitary GH(3) cells. MEM-mediated block of I-MEP in these cells is unlinked to its inhibition of glutamate-induced currents or ATP-sensitive le currents. The channel-suppressing properties of MEM might contribute to the underlying mechanisms by which it and its structurally related compounds affect neuronal or neuroendocrine function. (C) 2011 Elsevier Inc. All rights reserved.”
“Ankylosing spondylitis (AS) is a common, inflammatory rheumatic disease that primarily affects the axial skeleton and is associated with sacroiliitis, uveitis, and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid

arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine whether plasma from patients with www.selleckchem.com/Proteasome.html AS contained find more autoantibodies and, if so, characterize and quantify this response in comparison to patients with rheumatoid arthritis (RA) and healthy controls. Two high density

nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA, and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis to determine the patterns of signaling cascades or tissue origin. 44% of patients with ankylosing spondylitis demonstrated a broad autoantibody response, as compared with 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The autoantibody responses in the AS patients were targeted toward connective, skeletal, and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic acid programmable protein arrays constitute a powerful tool to study autoimmune diseases. Molecular & Cellular Proteomics 11: 10.1074/mcp.M9.00384, 1-10, 2012.

33-8 38]), believing

33-8.38]), believing LY2835219 supplier that H1N1 is a greater community concern than other diseases (OR: 1.77 [95% CI: 1.01-3.09]), believing that other methods of containment (eg, hand-washing, masks) are not as effective as the H1N1 vaccine (OR: 1.73 [95% CI: 1.06-2.83]), and a desire to promote influenza vaccination in the community (OR: 2.35 [95% CI: 1.53-3.61]).\n\nCONCLUSIONS: We found low acceptance of the H1N1 vaccine in our study population. Perceived influenza susceptibility, concern about

H1N1 disease, and confidence in vaccinations as preventive methods were associated with vaccine acceptance. Physician support for HIN1 vaccination will aid in increasing immunization coverage for this population, and health departments are perceived as ideal community locations for vaccine administration. Pediatrics 2011;127:S113-S119″
“Background: The search for gene

candidates in multifactorial diseases such as sarcoidosis can be based on the integration of linkage association data, gene expression data, and protein profile data from genomic, transcriptomic and proteomic studies, respectively.\n\nMaterial/Methods: In this study we performed a literature-based search for studies reporting such data, followed by integration of collected information. Different databases were examined-Medline, HugGE Navigator, ArrayExpress and Gene Expression Omnibus (GEO). Candidate genes were defined as genes which were reported in at least 2 different types of omics studies. Genes previously investigated in sarcoidosis were excluded from further analyses.\n\nResults: We identified 177 genes associated with sarcoidosis as potential new candidate genes. click here Subsequently, 9 gene candidates identified to overlap in 2 different types of studies (genomic, transcriptomic

and/or proteomic) were consistently reported in at least 3 studies: SERPINB1, FABP4, S100A8, HBEGF, IL7R, LRIG1, PTPN23, DPM2 and NUP214. These genes are involved in regulation of immune response, cellular proliferation, apoptosis, inhibition of protease activity, lipid metabolism. Exact biological functions of HBEGF, LRIG1, PTPN23, DPM2 and NUP214 remain to be completely elucidated.\n\nConclusions: We propose 9 candidate genes: SERPINB1, FABP4, S100A8, HBEGF, IL7R, LRIG1, PTPN23, DPM2 and NUP214, as genes with see more high potential for association with sarcoidosis.”
“Aim:\n\nHigh rates of paediatric ear, nose and throat (ENT) surgery persist. Little is known about its impact on health service utilisation. This study investigated whether children who had ENT surgery used more health services prior to surgery (excluding the perisurgery period), and, if so, whether surgery resulted in reduced utilisation.\n\nMethods:\n\nA retrospective population cohort study of health services use (measured by Medicare claims) by 6239 New South Wales children from the time of their birth in January 1990 until December 1997.

This work also discusses the morphological variation found in Rhy

This work also discusses the morphological variation found in Rhynchosia, and elucidates disparate data in the literature on seedlings of R. minima and R. phaseoloides.”
“Several anuran species

use multimodal signals to communicate in diverse social contexts. Our study describes acoustic and visual behaviours of the Small Torrent Frog (Micrixalus aff. saxicola), a diurnal frog endemic to the Western Ghats of India. During agonistic interactions males display advertisement calls, foot-flagging and tapping (foot lifting) high throughput screening behaviours to signal the readiness to defend perching sites in perennial streams. Results from a quantitative video analysis of male-male interactions indicate that foot-flagging displays were used as directional signals toward the opponent male, but were less abundant than calls. The acoustic and visual signals were not functionally linked. The call of Micrixalus aff. saxicola thereby did not act as an alert signal. Analysis of behavioural

transitions revealed that kicking behaviours (physical attacks) significantly elicited kicks from interacting males. We suggest that foot-flagging displays ritualized from this frequently observed fighting Cl-amidine technique to reduce physical attacks.”
“Background: MicroRNAs (miRNAs) are known to regulate the inflammatory response in various cell types. However, the ability of miRNAs to modulate dendritic cells (DCs) function for allergen immunotherapy is unclear. Objective: To assess the role of miR-23b in the regulation of ovalbumin (OVA)induced DC differentiation and function and to investigate the related molecular mechanisms.\n\nMethods: Bone marrow-derived dendritic cells (BMDCs) were generated from murine bone marrow progenitor cells and subsequently stimulated with OVA to examine the profile of miRNA expression. After transfection with miR-23b

reagents, DCs were evaluated for endocytic ability, surface marker expression, cytokine secretion and CD4+ T-cell differentiation. The possible roles of the Notch and NF-kappa B signalling pathways were also evaluated. Human monocytederived dendritic cells (MDDCs) were similarly evaluated as well.\n\nResults: Significant upregulation of miR-23b was observed in BMDCs pulsed with OVA. Following Selleck R406 miR-23b transfection, BMDCs showed decreased OVA uptake, increased IL-10 production, decreased IL-12 production and an enhanced capacity to promote FoxP3+ CD4+ T regulatory cells (Tregs) differentiation. In addition, inactivation of the Notch1 and NF-kappa B signalling pathways were observed. Conversely, inhibition of miR-23b in BMDCs resulted in the opposite effects. In human MDDCs, miRNA23b transfection similarly increased IL-10 and decreased IL-12 production, and that treated human MDDCs induced increased FoxP3+ CD4+ T cells.

If one does not account for this endogeneity, it appears that an

If one does not account for this endogeneity, it appears that an additional year of school exposure results in a greater BMI and a higher

probability of being overweight or obese. When we compare the weight outcomes of similar age children with one versus two years GW4869 cost of school exposure due to regulations on school starting age, the significant positive effects disappear, and most point estimates become negative, but insignificant. However, additional school exposure appears to improve weight outcomes of children for whom the transition to elementary school represents a more dramatic change in environment (those who spent less time in childcare prior to kindergarten). (C) 2011 Elsevier B.V. All rights reserved.”
“Purpose: A novel approach to a computer aided diagnosis system for the Parkinson’s disease is proposed. This tool is intended as a supporting tool for physicians, based on fully automated methods that lead to the classification of 123I-ioflupane SPECT images. Methods: I-123-ioflupane images from three different databases are used to train the system. The images are intensity and spatially normalized,

then subimages are extracted and a 3D gray-level co-occurrence matrix is computed over these subimages, allowing the characterization of the texture using Haralick texture features. Finally, different discrimination estimation methods are used to select a feature vector that can be used to train and test the classifier. Results: Using the leave-one-out cross-validation technique over these three databases, the system selleck chemicals llc achieves results up to a CH5183284 chemical structure 97.4% of accuracy, and 99.1% of sensitivity, with positive likelihood ratios over 27. Conclusions: The system presents

a robust feature extraction method that helps physicians in the diagnosis task by providing objective, operator-independent textural information about I-123-ioflupane images, commonly used in the diagnosis of the Parkinson’s disease. Textural features computation has been optimized by using a subimage selection algorithm, and the discrimination estimation methods used here makes the system feature-independent, allowing us to extend it to other databases and diseases. (C) 2014 American Association of Physicists in Medicine.”
“In the last several decades, developmental biology has clarified the molecular mechanisms of embryogenesis and organogenesis. In particular, it has demonstrated that the tool-kit genes essential for regulating developmental processes are not only highly conserved among species, but are also used as systems at various times and places in an organism to control distinct developmental events. Therefore, mutations in many of these tool-kit genes may cause congenital diseases involving morphological abnormalities.

Results: CT detected peritoneal seeding in 26/31 patients, 18

\n\nResults: CT detected peritoneal seeding in 26/31 patients, 18F-FDG-PET in 25/31 patients, and 18F-FDG-PET/MDCT in 30/31 patients, for a sensitivity of 88%, 88%, and 100%, respectively. False-positive findings were seen in MDCT in one patient, in 18F-FDG-PET in two patients, and in 18F-MDCT-PET/MDCT in one patient, for a specificity of 97%, https://www.selleckchem.com/products/gsk2879552-2hcl.html 94%, and 97%, respectively.\n\nConclusion: Fused 18F-FDG-PET/MDCT is superior to MDCT and

18F-FDG-PET alone for the detection of peritoneal carcinomatosis especially in small lesions and it offers exact anatomic information for surgical treatment. (C) 2007 Elsevier Ireland Ltd. All rights reserved.”
“The persistence of propanil in soil and aquatic environments along with the possible accumulation of toxic degradation products, SU5402 such as chloroanilines, is of environmental concern. In this work, a continuous small-scale bioprocess to degrade the herbicide propanil, its main catabolic by-product, 3,4-dichloroaniline (3,4-DCA), and the herbicide adjuvants is carried out. A microbial

consortium, constituted by nine bacterial genera, was selected. The isolated strains, identified by amplification and sequencing of their 16S rDNA, were: Acidovorax sp., Luteibacter (rhizovicinus), Xanthomonas sp., Flavobacterium sp., Variovorax sp., Acinetobacter (calcoaceticus), Pseudomonas sp., Rhodococcus sp., and Kocuria sp. The ability of the microbial consortium to degrade the herbicide was evaluated in a biofilm reactor at propanil loading rates ranging from 1.9 to 36.8 mg L-1 h(-1). Complete removal of propanil, 3,4-DCA, chemical oxygen demand and total organic carbon was obtained at propanil loading rates up to 24.9 mg L-1 h(-1). At higher loading rates, the removal efficiencies decayed. Four of the identified strains could grow individually in propanil, and 3,4-DCA: Pseudomonas

sp., Acinetobacter calcoaceticus, Rhodococcus sp., and Xanthomonas sp. The Kokuria strain grew on 3,4-DCA, but not on propanil. The first three bacteria Selleckchem URMC-099 have been related to biodegradation of phenyl urea herbicides or chlorinated anilines. Although some strains of the genera Xanthomonas and Kocuria have a role in the biodegradation of several xenobiotic compounds, as far as we know, there are no reports about degradation of propanil by Xanthomonas or 3,4-DCA by Kocuria species.”
“OBJECTIVES: A population-based study was performed to characterise the genotype and phenotype of drug-resistant tuberculosis (TB) in the year 2004-2005 in two Chinese rural counties with different durations of DOTS implementation, Deqing and Guanyun.\n\nMETHODS: Mycobacterium tuberculosis strains were isolated from respectively 164 and 187 patients registered at local TB dispensaries of Deqing and Guanyun. Drug susceptibility profiling and DNA sequencing were performed on the isolates.


“The overexpression of Hdm2 and HdmX is a common mechanism


“The overexpression of Hdm2 and HdmX is a common mechanism used by many tumor cells to inactive the p53 tumor suppressor pathway promoting cell survival. Targeting Hdm2 and HdmX has emerged Selleck SRT1720 as a validated therapeutic strategy for treating cancers with wild-type p53. Small linear peptides mimicking the N-terminal fragment of p53 have been shown to be potent Hdm2/HdmX antagonists. The potential therapeutic use of these peptides, however, is limited by their poor stability and bioavailability. Here, we report the engineering of the cyclotide MCoTI-I to efficiently antagonize intracellular

p53 degradation. The resulting cyclotide MCo-PMI was able to bind with low nanomolar affinity to both Hdm2 and HdmX, showed high stability in human serum, and was cytotoxic to wild-type p53 cancer cell lines by activating the p53 tumor suppressor https://www.selleckchem.com/products/lcl161.html pathway both in vitro and in vivo. These features make the cyclotide MCoTI-I an optimal scaffold for targeting intracellular protein-protein interactions.”
“Background:

Alcoholic hepatitis is the most florid presentation of alcohol-related liver disease. In its severe form, defined by a Maddrey’s discriminant function (DF) >= 32, the 28-day mortality rate is approximately 35%. A number of potential treatments have been subjected to clinical trials, of which two, corticosteroids and pentoxifylline, may have therapeutic benefit. The role of corticosteroids is controversial as trial results have been inconsistent, whereas the role of pentoxifylline requires confirmation as only one previous placebo-controlled trial has been published. Methods/design: STOPAH is a multicentre, double-blind, factorial (2 x 2) trial in which patients are randomised to one of four groups:\n\n1. Group A: placebo / placebo\n\n2. Group B: placebo / prednisolone\n\n3. Group C: pentoxifylline / placebo\n\n4. Group D: pentoxifylline / prednisolone\n\nThe trial aims to randomise 1,200 patients with severe alcoholic hepatitis, in order to provide sufficient power to determine whether

either of the two interventions is effective. The primary endpoint of the study is mortality at 28 days, with secondary check details endpoints being mortality at 90 days and 1 year. Discussion: STOPAH aims to be a definitive study to resolve controversy around the existing treatments for alcoholic hepatitis. Eligibility criteria are based on clinical parameters rather than liver biopsy, which are aligned with standard clinical practice in most hospitals. The use of a factorial design will allow two treatments to be evaluated in parallel, with efficient use of patient numbers to achieve high statistical power.”
“Background: The contrast between the low proportion of tuberculosis (TB) suspects referred from private practitioners in Bali province and the high volume of TB suspects seeking care at private practices suggests problems with TB suspect referral from private practitioners to the public health sector.

Distinct factors could account for the persistent gap observed be

Distinct factors could account for the persistent gap observed between natives’ and non-natives’ syntactic abilities: L1-L2 differences, AoA, proficiency, L2 immersion duration, L2 training duration. Although different theoretical approaches described the role of these several factors, not all studies using on-line measures have investigated them comprehensively and consistently. The present work reviews available ERP studies on L2 syntactic analysis in order to establish the relative weight of each factor on the time NU7441 inhibitor course of L2 processing. Logistic regression analyses were performed on the presence or absence of ERP

effects reported in response to L2 syntactic violations, including all the influential factors as categorical independent variables. The results showed that immersion duration has an influence on AZD9291 order the ERP correlates linked to early mechanisms of syntactic processing, while the global proficiency level has an impact on the ERP correlates related to late, language-monitoring activity. (C) 2015 Elsevier Ltd. All rights reserved.”
“Human immunodeficiency virus type 1 protease (HIV-1 PR) is an essential enzyme in the HIV-1 life cycle. As such, this protein represents a major drug target in AIDS therapy, but emerging resistance to antiretroviral inhibitor cocktails, caused by high viral mutation rates, represents a significant challenge in AIDS treatment. Many mutations are not located

within

the active site or binding pocket, nor they do significantly modify the three-dimensional structural organization of the enzyme; hence, the mechanism(s) by which they alter inhibitor affinity for the protease remains uncertain. In this article, we present an all-atom computational analysis of the dynamic residue-residue coordination between the active site residues and the rest of the protein and of the energetic properties of different HIV-1 PR complexes. We analyze both the wildtype form and mutated forms that induce drug resistance, In particular, the results show differences between the wild type and the mutants in their mechanism of dynamic coordination, in the signal propagation between the active site residues and the rest of the protein, and in the energy networks NCT-501 research buy responsible for the stabilization of the bound inhibitor conformation. Finally, we propose a dynamic and energetic explanation for HIV-1 protease drug resistance, and, through this model, we identify a possible new site that could be helpful in the design of a new family of HIV-1 PR allosteric inhibitors.”
“Dysfunctional tau accumulation is a major contributing factor in tauopathies, and the heat-shock protein 70 (Hsp70) seems to play an important role in this accumulation. Several reports suggest that Hsp70 proteins can cause tau degradation to be accelerated or slowed, but how these opposing activities are controlled is unclear.