bluuebunny/crossref_metadata_2025 huggingface dataset:
IntDOT Interactions with Core Sites during Integrative Recombination
Authors: Laprise Jennifer , Yoneji Sumiko , Gardner Jeffrey F.
Published: January 2013

Integrative and conjugative elements (ICEs), formerly called conjugative transposons, have been implicated in the proliferation of antibiotic resistance genes. CTnDOT is an extensively studied ICE found in
Bacteroides
spp. In addition to carrying resistance genes to both erythromycin and tetracycline, CTnDOT carries a gene that encodes a tyrosine recombinase called IntDOT that catalyzes integration into and excision out of the bacterial host chromosome. CTnDOT integrates into one of several known
attB
sites in the bacterial chromosome that consists of a pair of inverted repeat core sites called B and B′ in
attB
. The
attDOT
site contains the core sites and D and D′. These sites flank the overlap regions where strand exchanges occur. A notable feature of all known
attB
sites is the conservation of the B core site sequence, which is also found in the D core site of
attDOT
. In this study, we used a mutational analysis to establish the importance of this conserved sequence for integration and characterize the interaction of IntDOT with individual base pairs. We identified important T-A base pairs at position −5 in the B and D core sites and position +5 in the poorly conserved B′ core site that are important for integrative recombination. Base analog studies suggest that IntDOT may make specific contacts with the A residues in the major groove at positions −5 and +5. IntDOT interaction with the A at position −5 in the B core site is required for the first strand exchange.
YfdW and YfdU Are Required for Oxalate-Induced Acid Tolerance in Escherichia coli K-12
Authors: Fontenot Elise M. , Ezelle Karen E. , Gabreski Lauren N. , Giglio Eleanor R. , McAfee John M. , Mills Alexandria C. , Qureshi Maryam N. , Salmon Kristin M. , Toyota Cory G.
Published: January 2013

Escherichia colihas several mechanisms for surviving low-pH stress. We report that oxalic acid, a small-chain organic acid (SCOA), induces a moderate acid tolerance response (ATR) in two ways. Adaptation ofE. coliK-12 at pH 5.5 with 50 mM oxalate and inclusion of 25 mM oxalate in pH 3.0 minimal challenge medium separately conferred protection, with 67% ± 7% and 87% ± 17% survival after 2 h, respectively. The combination of oxalate adaptation and oxalate supplementation in the challenge medium resulted in increased survival over adaptation or oxalate in the challenge medium alone. The enzymes YfdW, a formyl coenzyme A (CoA) transferase, and YfdU, an oxalyl-CoA decarboxylase, are required for the adaptation effect but not during challenge. Unlike other SCOAs, this oxalate ATR is not a part of the RpoS regulon but appears to be linked to the signal protein GadE. We theorize that this oxalate ATR could enhance the pathogenesis of virulentE. coliconsumed with oxalate-containing foods like spinach.
Aeromonas hydrophila Lateral Flagellar Gene Transcriptional Hierarchy
Authors: Wilhelms Markus , Gonzalez Victor , Tomás Juan M. , Merino Susana
Published: January 2013

Aeromonas hydrophila
AH-3 lateral flagella are not assembled when bacteria grow in liquid media; however, lateral flagellar genes are transcribed. Our results indicate that
A. hydrophila
lateral flagellar genes are transcribed at three levels (class I to III genes) and share some similarities with, but have many important differences from, genes of
Vibrio parahaemolyticus
.
A. hydrophila
lateral flagellum class I gene transcription is σ
70
dependent, which is consistent with the fact that lateral flagellum is constitutively transcribed, in contrast to the characteristics of
V. parahaemolyticus.
The fact that multiple genes are included in class I highlights that lateral flagellar genes are less hierarchically transcribed than polar flagellum genes. The
A. hydrophila lafK
-
fliEJ
L
gene cluster (where the subscript L distinguishes genes for lateral flagella from those for polar flagella) is exclusively from class I and is in
V. parahaemolyticus
class I and II. Furthermore, the
A. hydrophila flgAMN
L
cluster is not transcribed from the σ
54
/LafK-dependent promoter and does not contain class II genes. Here, we propose a gene transcriptional hierarchy for the
A. hydrophila
lateral flagella.
Functional Characterization of Clostridium difficile Spore Coat Proteins
Authors: Permpoonpattana Patima , Phetcharaburanin Jutarop , Mikelsone Anna , Dembek Marcin , Tan Sisareuth , Brisson Marie-Clémence , La Ragione Roberto , Brisson Alain R. , Fairweather Neil , Hong Huynh A. , Cutting Simon M.
Published: January 2013

Spores of
Clostridium difficile
play a key role in the dissemination of this important human pathogen, and until recently little has been known of their functional characteristics. Genes encoding six spore coat proteins (
cotA
,
cotB
,
cotCB
,
cotD
,
cotE
, and
sodA
) were disrupted by ClosTron insertional mutagenesis. Mutation of one gene,
cotA
, presented a major structural defect in spore assembly, with a clear misassembly of the outermost layers of the spore coat. The CotA protein is most probably subject to posttranslational modification and could play a key role in stabilizing the spore coat. Surprisingly, mutation of the other spore coat genes did not affect the integrity of the spore, although for the
cotD
,
cotE
, and
sodA
mutants, enzyme activity was reduced or abolished. This could imply that these enzymatic proteins are located in the exosporium or alternatively that they are structurally redundant. Of the spore coat proteins predicted to carry enzymatic activity, three were confirmed to be enzymes using both
in vivo
and
in vitro
methods, the latter using recombinant expressed proteins. These were a manganese catalase, encoded by
cotD
, a superoxide dismutase (SOD), encoded by
sodA
, and a bifunctional enzyme with peroxiredoxin and chitinase activity, encoded by
cotE
. These enzymes being exposed on the spore surface would play a role in coat polymerization and detoxification of H
2
O
2
. Two additional proteins, CotF (a tyrosine-rich protein and potential substrate for SodA) and CotG (a putative manganese catalase) were shown to be located at the spore surface.
Effects of H
2
and Formate on Growth Yield and Regulation of Methanogenesis in Methanococcus maripaludis
Authors: Costa Kyle C. , Yoon Sung Ho , Pan Min , Burn June A. , Baliga Nitin S. , Leigh John A.
Published: January 2013

Hydrogenotrophic methanogenic
Archaea
are defined by an H
2
requirement for growth. Despite this requirement, many hydrogenotrophs are also capable of growth with formate as an electron donor for methanogenesis. While certain responses of these organisms to hydrogen availability have been characterized, responses to formate starvation have not been reported. Here we report that during continuous culture of
Methanococcus maripaludis
under defined nutrient conditions, growth yields relative to methane production decreased markedly with either H
2
excess or formate excess. Analysis of the growth yields of several mutants suggests that this phenomenon occurs independently of the storage of intracellular carbon or a transcriptional response to methanogenesis. Using microarray analysis, we found that the expression of genes encoding coenzyme F
420
-dependent steps of methanogenesis, including one of two formate dehydrogenases, increased with H
2
starvation but with formate occurred at high levels regardless of limitation or excess. One gene, encoding H
2
-dependent methylene-tetrahydromethanopterin dehydrogenase, decreased in expression with either H
2
limitation or formate limitation. Expression of genes for the second formate dehydrogenase, molybdenum-dependent formylmethanofuran dehydrogenase, and molybdenum transport increased specifically with formate limitation. Of the two formate dehydrogenases, only the first could support growth on formate in batch culture where formate was in excess.
Novel Modulators Controlling Entry into Sporulation in Bacillus subtilis
Authors: Garti-Levi Sharon , Eswara Ashlee , Smith Yoav , Fujita Masaya , Ben-Yehuda Sigal
Published: January 2013

Upon nutrient deprivation,
Bacillus subtilis
initiates the developmental process of sporulation by integrating environmental and extracellular signals. These signals are channeled into a phosphorelay ultimately activating the key transcriptional regulator of sporulation, Spo0A. Subsequently, phosphorylated Spo0A regulates the expression of genes required for sporulation to initiate. Here we identified a group of genes whose transcription levels are controlled by Spo0A during exponential growth. Among them, three upregulated genes, termed
sivA
,
sivB
(
bslA
), and
sivC
, encode factors found to inhibit Spo0A activation. We furthermore show that the Siv factors operate by reducing the activity of histidine kinases located at the top of the sporulation phosphorelay, thereby decreasing Spo0A phosphorylation. Thus, we demonstrate the existence of modulators, positively controlled by Spo0A, which inhibit inappropriate entry into the costly process of sporulation, when conditions are favorable for exponential growth.
Coordination of FocA and Pyruvate Formate-Lyase Synthesis in Escherichia coli Demonstrates Preferential Translocation of Formate over Other Mixed-Acid Fermentation Products
Authors: Beyer Lydia , Doberenz Claudia , Falke Dörte , Hunger Doreen , Suppmann Bernhard , Sawers R. Gary
Published: January 2013

Enterobacteria such as
Escherichia coli
generate formate, lactate, acetate, and succinate as major acidic fermentation products. Accumulation of these products in the cytoplasm would lead to uncoupling of the membrane potential, and therefore they must be either metabolized rapidly or exported from the cell.
E. coli
has three membrane-localized formate dehydrogenases (FDHs) that oxidize formate. Two of these have their respective active sites facing the periplasm, and the other is in the cytoplasm. The bidirectional FocA channel translocates formate across the membrane delivering substrate to these FDHs. FocA synthesis is tightly coupled to synthesis of pyruvate formate-lyase (PflB), which generates formate. In this study, we analyze the consequences on the fermentation product spectrum of altering FocA levels, uncoupling FocA from PflB synthesis or blocking formate metabolism. Changing the
focA
translation initiation codon from GUG to AUG resulted in a 20-fold increase in FocA during fermentation and an ∼3-fold increase in PflB. Nevertheless, the fermentation product spectrum throughout the growth phase remained similar to that of the wild type. Formate, acetate, and succinate were exported, but only formate was reimported by these cells. Lactate accumulated in the growth medium only in mutants lacking FocA, despite retaining active PflB, or when formate could not be metabolized intracellularly. Together, these results indicate that FocA has a strong preference for formate as a substrate
in vivo
and not other acidic fermentation products. The tight coupling between FocA and PflB synthesis ensures adequate substrate delivery to the appropriate FDH.
Exoprotein Production Correlates with Morphotype Changes of Nonmotile Shewanella oneidensis Mutants
Authors: Shi Miaomiao , Wu Lin , Xia Yu , Chen Haijiang , Luo Qixia , Sun Linlin , Gao Haichun
Published: January 2013

We report a previously undescribed mechanism for the rugose morphotype in
Shewanella oneidensis
, a research model for investigating redox transformations of environmental contaminants. Bacteria may form smooth or rugose colonies on agar plates. In general, conversion from the smooth to rugose colony morphotype is attributed to increased production of exopolysaccharide (EPS). In this work, we discovered that aflagellate
S. oneidensis
mutants grew into rugose colonies, whereas those with nonfunctional flagellar filaments remained smooth. EPS production was not altered in either case, but mutants with the rugose morphotype showed significantly reduced exoprotein secretion. The idea that exoproteins at a reduced level correlate with rugosity gained support from smooth suppressor strains of an aflagellate rugose
fliD
(encoding the capping protein) mutant, which restored the exoprotein level to the levels of the wild-type and mutant strains with a smooth morphotype. Further analyses revealed that SO1072 (a putative GlcNAc-binding protein) was one of the highly upregulated exoproteins in these suppressor strains. Most intriguingly, this study identified a compensatory mechanism of SO1072 to flagellins possibly mediated by bis-(3′-5′)-cyclic dimeric GMP.
The Cpx Stress Response Confers Resistance to Some, but Not All, Bactericidal Antibiotics
Authors: Mahoney Tara F. , Silhavy Thomas J.
Published: January 2013

It has recently been suggested that bactericidal antibiotics, including aminoglycoside antibiotics (AGAs), and toxic small molecules, such as hydroxyurea (HU), kill bacteria the same way, namely, by generating reactive oxygen species (ROS) via a process requiring activation of the Cpx stress response. We suggest an opposite, protective role for Cpx. We have confirmed the initial finding that
cpxA
null mutations confer resistance to HU. However, the two-component sensor CpxA is both a kinase and a phosphatase, and previous work from our lab has shown that removing CpxA can activate the stress response owing to buildup of the phosphorylated response regulator (CpxR∼P) that occurs in the absence of the phosphatase activity. We show that a dominant
cpxA
* mutation that constitutively activates the Cpx stress response confers a high level of resistance to both HU and AGAs in a CpxR-dependent manner. In contrast, inactivating the CpxR response regulator by mutating the phosphorylation site (D51A) or the putative DNA-binding motif (M199A) does not increase resistance to HU or AGAs. Taken together, these results demonstrate that activation of the Cpx stress response can protect cells from HU and AGAs. However, the Cpx response does not increase resistance to all classes of bactericidal antibiotics, as the
cpxA
* mutants are not significantly more resistant to fluoroquinolones or β-lactams than wild-type cells. Thus, it seems unlikely that all bactericidal antibiotics kill by the same mechanism.
Topology and Accessibility of Germination Proteins in the Bacillus subtilis Spore Inner Membrane
Authors: Korza George , Setlow Peter
Published: January 2013

Access to a membrane-impermeant biotinylation reagent as well as protease sensitivity was used to determine germination proteins' topology in the inner membrane (IM) of decoated dormant spores and intact germinated
Bacillus subtilis
spores. The proteins examined were four nutrient germinant receptor (GR) subunits, the GerD protein, essential for normal GR-dependent spore germination, the SpoVAD protein, essential for dipicolinic acid movement across the IM, the SleB cortex-lytic enzyme, and the YpeB protein, essential for SleB assembly in spores, as well as green fluorescent protein (GFP) in the spore core. GerD and SpoVAD as well as GFP in the spore were not biotinylated in decoated dormant spores. However, GR subunits, SleB, and YpeB were biotinylated 4 to 36% in decoated dormant spores, although these levels were not increased by higher biotinylation reagent concentrations or longer reaction times. In contrast, the germination proteins were largely biotinylated in germinated spores, although GFP was not. All of the germination proteins in the germinated spore's IM, but not spore core GFP, were largely sensitive to an exogenous protease. These results, coupled with predicted or experimentally determined structural data, indicate that (i) these germination proteins are at least partially and in some cases completely on the outer surface of the spore's IM and (ii) there is significant reorganization of these germination proteins' structure or environment in the IM during spore germination.
Severe epistaxis after nasogastric tube insertion requiring arterial embolisation
Authors: Paul Vishesh , Kupfer Yizhak , Tessler Sidney
Published: January 2013

A 53-year-old dialysis patient was admitted with symptoms of a respiratory tract infection, abdominal pain and vomiting. She aspirated and required intubation. A nasogastric tube was placed with slight difficulty and the patient developed severe epistaxis. The bleeding could not be controlled with mechanical pressure and nasal packing. Angiography revealed extravasation from a pseudoaneurysm arising from the inferior pharyngeal branch of the ascending pharyngeal trunk. The vessel was successfully embolised with cessation of bleeding. We emphasise that even a seemingly easy procedure like insertion of a nasogastric tube, can lead to a life-threatening complication.
Methylene blue reverses recalcitrant shock in β-blocker and calcium channel blocker overdose
Authors: Aggarwal Nidhi , Kupfer Yizhak , Seneviratne Chanaka , Tessler Sidney
Published: January 2013

β-blocker and calcium channel blocker toxicity generally present with bradycardia and hypotension. A 69-year-old woman presented after a suicide attempt with a β-blocker and calcium channel blocker overdose. Her blood pressure was 69/35 mm Hg and her HR was in the 40s. She was treated with calcium chloride, glucagon, a dextrose–insulin infusion and three vasopressors, but remained hypotensive. She suffered two cardiac arrests and required a transvenous pacemaker. When all interventions failed, she was started on a methylene blue infusion for refractory vasodilatory shock which resulted in a dramatic improvement in her blood pressure. The patient was successfully weaned off all vasopressors and from mechanical ventilation without any end-organ damage.
Snake bite-induced leucoencephalopathy
Authors: Chaudhary Shyam Chand , Sawlani Kamal Kumar , Malhotra Hardeep Singh , Singh Jitendra
Published: January 2013

Snake bite is an important cause of mortality and morbidity in India with an estimated 35 000–50 000 fatal bites occurring annually. Neurological deficits following vasculotoxic snake bite are either due to intracranial haemorrhage or subarachnoid bleed as a result of consumption coagulopathy. However, ischaemic strokes and acute disseminated encephalomyelitis have been reported occasionally. We hereby report a case of snake bite leading to leucoencephalopathy.
Hidden treasure in an endoscopically retrieved oesophageal trichobezoar
Authors: Renji Elizabeth , Nathan Anand K , Dalzell Mark A
Published: January 2013

A 12-year-old girl with Smith-Lemli-Opitz syndrome and gastrostomy dependency presented with multiple episodes of coffee ground vomits. An upper gastrointestinal endoscopy revealed a trichobezoar in the lower oesophagus, with a ‘hidden treasure’—a retained end of a G tube at the core. Endoscopic retrieval led to resolution of symptoms. Literature is scant with only one previous report of an oesophageal trichobezoar. Techniques of removal of percutaneous endoscopic gastrostomy in children are reviewed. The pathogenesis, preventative measures and management for oesophageal trichobezoars are discussed.
Evidence for the effectiveness of electrophysical modalities for treatment of medial and lateral epicondylitis: a systematic review
Authors: Dingemanse Rudi , Randsdorp Manon , Koes Bart W , Huisstede Bionka M A
Published: January 2013

Background

Several treatments are available to treat epicondylitis. Among these are instrumental electrophysical modalities, ranging from ultrasound, extracorporeal shock wave therapy (ESWT), transcutaneous electrical nerve stimulation (TENS) to laser therapy, commonly used to treat epicondylitis.

Objectives

To present an evidence-based overview of the effectiveness of electrophysical modality treatments for both medial and lateral epicondylitis (LE).

Methods

Searches in PubMed, EMBASE, CINAHL and Pedro were performed to identify relevant randomised clinical trials (RCTs) and systematic reviews. Two reviewers independently extracted data and assessed the methodological quality. A best-evidence synthesis was used to summarise the results.

Results

A total of 2 reviews and 20 RCTs were included, all of which concerned LE. Different electrophysical regimes were evaluated: ultrasound, laser, electrotherapy, ESWT, TENS and pulsed electromagnetic field therapy. Moderate evidence was found for the effectiveness of ultrasound versus placebo on mid-term follow-up. Ultrasound plus friction massage showed moderate evidence of effectiveness versus laser therapy on short-term follow-up. On the contrary, moderate evidence was found in favour of laser therapy over plyometric exercises on short-term follow-up. For all other modalities only limited/conflicting evidence for effectiveness or evidence of no difference in effect was found.

Conclusions

Potential effectiveness of ultrasound and laser for the management of LE was found. To draw more definite conclusions high-quality RCTs examining different intensities are needed as well as studies focusing on long-term follow-up results.
The RUC: a primer for neurointerventionalists
Authors: Hirsch Joshua A , Silva Ezequiel , Nicola Gregory N , Barr Robert M , Bello Jacqueline A , Manchikanti Laxmaiah , Donovan William D
Published: January 2013

The Relative Value Scale Update Committee (RUC) plays a critical role in determining physician payment. When the Centers for Medicare and Medicaid Services (CMS) transitioned to paying physicians based on the Resource-Based Relative Value Scale, the American Medical Association developed this unique multispecialty committee. Physicians at the RUC determine the resources required to provide physician services and recommend appropriate payment for those services. The RUC then submits its recommendations to CMS. Physicians have thus been important in determining relative value and hence payment for the services they provide.
Making Slaughterhouses More Humane for Cattle, Pigs, and Sheep
Authors: Grandin Temple
Published: January 2013

When a stunning method is being evaluated, it is essential that the animal-handling and restraint methods that are used with it are also examined. This makes it possible to determine the effect of the entire system on animal welfare. Cattle, pigs, and sheep will move easily through the races at a slaughter plant if visual distractions such as reflections on shiny metal, dangling chains, moving equipment, or people up ahead are removed. The most important scientific research on captive bolt, CO2, and electrical stunning methods is reviewed. A common mistake made by people evaluating insensibility is to misinterpret reflexive leg kicks as a sign of return to sensibility. When religious slaughter is being evaluated, the variable of how the animal is restrained must be separated from the variable of slaughter without stunning. Slaughter can be done with a high level of animal welfare.
Classification and Comparison of Small RNAs from Plants
Authors: Axtell Michael J.
Published: January 2013

Regulatory small RNAs, which range in size from 20 to 24 nucleotides, are ubiquitous components of endogenous plant transcriptomes, as well as common responses to exogenous viral infections and introduced double-stranded RNA (dsRNA). Endogenous small RNAs derive from the processing of helical RNA precursors and can be categorized into several groups based on differences in biogenesis and function. A major distinction can be observed between small RNAs derived from single-stranded precursors with a hairpin structure [referred to here as hairpin RNAs (hpRNAs)] and those derived from dsRNA precursors [small interfering RNAs (siRNAs)]. hpRNAs in plants can be divided into two secondary groups: microRNAs and those that are not microRNAs. The currently known siRNAs fall mostly into one of three secondary groups: heterochromatic siRNAs, secondary siRNAs, and natural antisense transcript siRNAs. Tertiary subdivisions can be identified within many of the secondary classifications as well. Comparisons between the different classes of plant small RNAs help to illuminate key goals for future research.
Endoplasmic Reticulum Stress Responses in Plants
Authors: Howell Stephen H.
Published: January 2013

Endoplasmic reticulum (ER) stress is of considerable interest to plant biologists because it occurs in plants subjected to adverse environmental conditions. ER stress responses mitigate the damage caused by stress and confer levels of stress tolerance to plants. ER stress is activated by misfolded proteins that accumulate in the ER under adverse environmental conditions. Under these conditions, the demand for protein folding exceeds the capacity of the system, which sets off the unfolded protein response (UPR). Two arms of the UPR signaling pathway have been described in plants: one that involves two ER membrane–associated transcription factors (bZIP17 and bZIP28) and another that involves a dual protein kinase (RNA-splicing factor IRE1) and its target RNA (bZIP60). Under mild or short-term stress conditions, signaling from IRE1 activates autophagy, a cell survival response. But under severe or chronic stress conditions, ER stress can lead to cell death.
Plant Protein Interactomes
Authors: Braun Pascal , Aubourg Sébastien , Van Leene Jelle , De Jaeger Geert , Lurin Claire
Published: January 2013

Protein-protein interactions are a critical element of biological systems, and the analysis of interaction partners can provide valuable hints about unknown functions of a protein. In recent years, several large-scale protein interaction studies have begun to unravel the complex networks through which plant proteins exert their functions. Two major classes of experimental approaches are used for protein interaction mapping: analysis of direct interactions using binary methods such as yeast two-hybrid or split ubiquitin, and analysis of protein complexes through affinity purification followed by mass spectrometry. In addition, bioinformatics predictions can suggest interactions that have evaded detection by other methods or those of proteins that have not been investigated. Here we review the major approaches to construct, analyze, use, and carry out quality control on plant protein interactome networks. We present experimental and computational approaches for large-scale mapping, methods for validation or smaller-scale functional studies, important bioinformatics resources, and findings from recently published large-scale plant interactome network maps.
Potassium Transport and Signaling in Higher Plants
Authors: Wang Yi , Wu Wei-Hua
Published: January 2013

As one of the most important mineral nutrient elements, potassium (K+) participates in many plant physiological processes and determines the yield and quality of crop production. In this review, we summarize K+ signaling processes and K+ transport regulation in higher plants, especially in plant responses to K+-deficiency stress. Plants perceive external K+ fluctuations and generate the initial K+ signal in root cells. This signal is transduced into the cytoplasm and encoded as Ca2+ and reactive oxygen species signaling. K+-deficiency-induced signals are subsequently decoded by cytoplasmic sensors, which regulate the downstream transcriptional and posttranslational responses. Eventually, plants produce a series of adaptive events in both physiological and morphological alterations that help them survive K+ deficiency.
The Spatial Organization of Metabolism Within the Plant Cell
Authors: Sweetlove Lee J. , Fernie Alisdair R.
Published: January 2013

Identifying the correct subcellular locations for all enzymes and metabolites in plant metabolic networks is a major challenge, but is critically important for the success of the new generation of large-scale metabolic models that are driving a network-level appreciation of metabolic behavior. Even though the subcellular compartmentation of many central metabolic processes is thought to be well understood, recent gene-by-gene studies have revealed several unexpected enzyme localizations. Metabolite transport between subcellular compartments is crucial because it fundamentally affects the metabolic network structure. Although new metabolite transporters are being steadily identified, modeling work suggests that we have barely scratched the surface of the catalog of intracellular metabolite transporter proteins. In addition to compartmentation among organelles, it is increasingly apparent that microcompartment formation via the interactions of enzyme groups with intracellular membranes, the cytoskeleton, or other proteins is an important regulatory mechanism. In particular, this mechanism can promote metabolite channeling within the metabolic microcompartment, which can help control reaction specificity as well as dictate flux routes through the network. This has clear relevance for both synthetic biology in general and the engineering of plant metabolic networks in particular.
Quitting Drugs: Quantitative and Qualitative Features
Authors: Heyman Gene M.
Published: January 2013

According to the idea that addiction is a chronic relapsing disease, remission is at most a temporary state. Either addicts never stop using drugs, or if they do stop, remission is short lived. However, research on remission reveals a more complex picture. In national epidemiological surveys that recruited representative drug users, remission rates varied widely and were markedly different for legal and illegal drugs and for different racial/ethnic groups. For instance, the half-life for cocaine dependence was four years, but for alcohol dependence it was 16 years, and although most dependent cocaine users remitted before age 30, about 5% remained heavy cocaine users well into their forties. Although varied, the remission results were orderly. An exponential growth curve closely approximated the cumulative frequency of remitting for different drugs and different ethnic/racial groups. Thus, each year a constant proportion of those still addicted remitted, independent of the number of years since the onset of dependence.
Psychosocial Treatments for Schizophrenia
Authors: Mueser Kim T. , Deavers Frances , Penn David L. , Cassisi Jeffrey E.
Published: January 2013

The current state of the literature regarding psychosocial treatments for schizophrenia is reviewed within the frameworks of the recovery model of mental health and the expanded stress-vulnerability model. Interventions targeting specific domains of functioning, age groups, stages of illness, and human service system gaps are classified as evidence-based practices or promising practices according to the extent to which their efficacy is currently supported by meta-analyses and individual randomized controlled trials (RCTs). Evidence-based practices include assertive community treatment (ACT), cognitive behavior therapy (CBT) for psychosis, cognitive remediation, family psychoeducation, illness self-management training, social skills training, and supported employment. Promising practices include cognitive adaptive therapy, CBT for posttraumatic stress disorder, first-episode psychosis intervention, healthy lifestyle interventions, integrated treatment for co-occurring disorders, interventions targeting older individuals, peer support services, physical disease management, prodromal stage intervention, social cognition training, supported education, and supported housing. Implications and future directions are discussed.
The Manufacture of Recovery
Authors: Braslow Joel Tupper
Published: January 2013

Recovery (also known as the “recovery orientation,” “recovery vision,” or “recovery philosophy”) has been the dominant paradigm shaping current mental health policy for the past decade. It is claimed to be a revolutionary departure from the past and a guide to policy that will transform outcomes of severe mental illness. This review looks critically at the history of recovery and examines the ways in which this history has shaped the values, beliefs, and practices of current recovery-based policies. Recovery is a treatment philosophy that emerged from the ruins of deinstitutionalization and the psychopharmaceutical revolution. Yet paradoxically, recovery reflects many of the same ideas that made deinstitutionalization and the era of psychopharmacology possible. Further, history reveals how the recovery movement is deeply indebted to and embedded within the sociocultural values of neoliberalism that have shaped public policy since the presidential election of Ronald Reagan in 1980.
Colloidal Particles: Crystals, Glasses, and Gels
Authors: Lu (陸述義) Peter J. , Weitz David A.
Published: January 2013

Colloidal particles are microscopic solid particles suspended in a fluid. Colloids are small enough that thermal energy drives their dynamics and ensures equilibration with the suspending fluid; they are also large enough that their positions and motions can be measured precisely using optical methods, such as light scattering and laser-scanning confocal fluorescence microscopy. Colloidal suspensions are a powerful model system for the study of other phenomena in condensed matter physics, where the collective phase behavior of the solid particles mimics that of other condensed systems. We review three classes of interacting colloidal particles, crystals, glasses, and gels, each of which represents fascinating properties of colloidal particles as well as a model for more general types of materials and their behavior.
Bridging Lattice-Scale Physics and Continuum Field Theory with Quantum Monte Carlo Simulations
Authors: Kaul Ribhu K. , Melko Roger G. , Sandvik Anders W.
Published: January 2013

We discuss designer Hamiltonians—lattice models tailored to be free from sign problems (“de-signed”) when simulated with quantum Monte Carlo (QMC) methods but which still host complex many-body states and quantum phase transitions of interest in condensed matter physics. We focus on quantum spin systems in which competing interactions lead to nonmagnetic ground states. These states and the associated quantum phase transitions can be studied in great detail, enabling direct access to universal properties and connections with low-energy effective quantum field theories. As specific examples, we discuss the transition from a Néel antiferromagnet to either a uniform quantum paramagnet or a spontaneously symmetry-broken valence-bond solid (VBS) in SU(2) and SU(N) invariant spin models. We also discuss anisotropic (XXZ) systems harboring topological Z2 spin liquids and the XY* transition. We briefly review recent progress on QMC algorithms, including ground-state projection in the valence-bond basis and direct computation of the Renyi variants of the entanglement entropy.
Fluctuations, Linear Response, and Currents in Out-of-Equilibrium Systems
Authors: Ciliberto S. , Gomez-Solano R. , Petrosyan A.
Published: January 2013

In this review we discuss, from an experimental point of view, several concepts of statistical mechanics for systems that are out of equilibrium either because they are driven by external forces or because they are slowly relaxing toward equilibrium. We focus on the case where the mean injected energy is of the order of thermal fluctuations, which therefore cannot be neglected. We first introduce the main concepts of fluctuation theorems (FTs) for work and heat using measurements of (a) a harmonic oscillator driven out of equilibrium by an external force and (b) a colloidal particle trapped in a time-dependent double-well potential. We use the example of the Brownian particle to analyze the problem of the fluctuation-dissipation relation ( FDR ) in out-of-equilibrium systems. We next study the fluctuations of the position of a Brownian particle inside an aging gelatin after a fast quench. Using the experimental data of this experiment, we show that the mean heat flux is quantitatively related to the violation of the equilibrium fluctuation-dissipation theorem or equivalently to the entropy production rate. Finally, we discuss briefly the problems and the new directions for the stochastic thermodynamics.
Why I Haven't Retired
Authors: Geballe Theodore H.
Published: January 2013

What is written below is, as requested by the editor of AR Condensed Matter Physics, a set of recollections and insights gained from my personal trajectory that starts from my earliest years and continues on until now. I have been a participant in the growth of solid state physics from its early quantum insights to the highly popular foci of today’s vibrant condensed matter science community, while working at three institutions that helped spearhead this growth—UC Berkeley, Bell Labs, and Stanford University. It is rare to be actively involved in any creative enterprise for more than six decades. I credit my good fortune to stimulating science; great students and colleagues; a happy home; warm friendships; and, evidently, to my having inherited good genes.
Molecular Control of Steady-State Dendritic Cell Maturation and Immune Homeostasis
Authors: Hammer Gianna Elena , Ma Averil
Published: January 2013

Dendritic cells (DCs) are specialized sentinels responsible for coordinating adaptive immunity. This function is dependent upon coupled sensitivity to environmental signs of inflammation and infection to cellular maturation—the programmed alteration of DC phenotype and function to enhance immune cell activation. Although DCs are thus well equipped to respond to pathogens, maturation triggers are not unique to infection. Given that immune cells are exquisitely sensitive to the biological functions of DCs, we now appreciate that multiple layers of suppression are required to restrict the environmental sensitivity, cellular maturation, and even life span of DCs to prevent aberrant immune activation during the steady state. At the same time, steady-state DCs are not quiescent but rather perform key functions that support homeostasis of numerous cell types. Here we review these functions and molecular mechanisms of suppression that control steady-state DC maturation. Corruption of these steady-state operatives has diverse immunological consequences and pinpoints DCs as potent drivers of autoimmune and inflammatory disease.
Broadly Neutralizing Antiviral Antibodies
Authors: Corti Davide , Lanzavecchia Antonio
Published: January 2013

A fascinating aspect of viral evolution relates to the ability of viruses to escape the adaptive immune response. The widely held view has been that the great variability of viral glycoproteins would be an absolute obstacle to the development of antibody-based therapies or vaccines that could confer broad and long-lasting protection. In the past five years, new approaches have been developed to interrogate human memory B cells and plasma cells with high efficiency and to isolate several broadly neutralizing antiviral antibodies against highly variable pathogens such as HIV-1 and influenza virus. These antibodies not only provide new tools for prophylaxis and therapy for viral diseases but also identify conserved epitopes that may be used to design new vaccines capable of conferring broader protection.
Human Hemato-Lymphoid System Mice: Current Use and Future Potential for Medicine
Authors: Rongvaux Anthony , Takizawa Hitoshi , Strowig Till , Willinger Tim , Eynon Elizabeth E. , Flavell Richard A. , Manz Markus G.
Published: January 2013

To directly study complex human hemato-lymphoid system physiology and respective system-associated diseases in vivo, human-to-mouse xenotransplantation models for human blood and blood-forming cells and organs have been developed over the past three decades. We here review the fundamental requirements and the remarkable progress made over the past few years in improving these systems, the current major achievements reached by use of these models, and the future challenges to more closely model and study human health and disease and to achieve predictive preclinical testing of both prevention measures and potential new therapies.
Signaling by the Phosphoinositide 3-Kinase Family in Immune Cells
Authors: Okkenhaug Klaus
Published: January 2013

Phosphoinositide 3-kinases (PI3Ks) control many important aspects of immune cell development, differentiation, and function. Mammals have eight PI3K catalytic subunits that are divided into three classes based on similarities in structure and function. Specific roles for the class I PI3Ks have been broadly investigated and are relatively well understood, as is the function of their corresponding phosphatases. More recently, specific roles for the class II and class III PI3Ks have emerged. Through vertebrate evolution and in parallel with the evolution of adaptive immunity, there has been a dramatic increase not only in the genes for PI3K subunits but also in genes for phosphatases that act on 3-phosphoinositides and in 3-phosphoinositide-binding proteins. Our understanding of the PI3Ks in immunity is guided by fundamental discoveries made in simpler model organisms as well as by appreciating new adaptations of this signaling module in mammals in general and in immune cells in particular.
Electroplating Using Ionic Liquids
Authors: Abbott Andrew P. , Frisch Gero , Ryder Karl S.
Published: January 2013

Electroplating is a key technology in many large-scale industrial applications such as corrosion-resistant and decorative coatings. Issues with current aqueous processes, such as toxicity of reagents and low current efficiencies, can often be overcome by using ionic liquids, and this approach has turned ionometallurgy into a fast-growing area of research. This review outlines the interactions in ionic liquids that are responsible for the advantageous properties of these solvents in electroplating. It summarizes recent research in which these properties have been analyzed or exploited and highlights fundamental issues in research and technology that need to be addressed.
Molecular Imaging Using X-Ray Free-Electron Lasers
Authors: Barty Anton , Küpper Jochen , Chapman Henry N.
Published: January 2013

The opening of hard X-ray free-electron laser facilities, such as the Linac Coherent Light Source (LCLS) at SLAC National Accelerator Laboratory in the United States, has ushered in a new era in structural determination. With X-ray pulse durations down to 10 fs or shorter, and up to 1013transversely coherent photons per pulse in a narrow spectral bandwidth, focused irradiances of 1018to 1021W cm−2or higher can be produced at X-ray energies ranging from 500 eV to 10 keV. New techniques for determining the structure of systems that cannot be crystallized and for studying the time-resolved behavior of irreversible reactions at femtosecond timescales are now available.
Chemical Aspects of the Extractive Methods of Ambient Ionization Mass Spectrometry
Authors: Badu-Tawiah Abraham K. , Eberlin Livia S. , Ouyang Zheng , Cooks R. Graham
Published: January 2013

Ambient ionization techniques allow complex chemical samples to be analyzed in their native state with minimal sample preparation. This brings the obvious advantages of simplicity, speed, and versatility to mass spectrometry: Desorption electrospray ionization (DESI), for example, is used in chemical imaging for tumor margin diagnosis. This review on the extractive methods of ambient ionization focuses on chemical aspects, mechanistic considerations, and the accelerated chemical reactions occurring in charged liquid droplets generated in the spray process. DESI uses high-velocity solvent droplets to extract analytes from surfaces. Nano-DESI employs liquid microjunctions for analyte dissolution, whereas paper-spray ionization uses DC potentials applied to wet porous material such as paper or biological tissue to field emit charged analyte-containing solvent droplets. These methods also operate in a reactive mode in which added reagents allow derivatization during ionization. The accelerated reaction rates seen in charged microdroplets are useful in small-scale rapid chemical synthesis.
Dynamic Nuclear Polarization Methods in Solids and Solutions to Explore Membrane Proteins and Membrane Systems
Authors: Cheng Chi-Yuan , Han Songi
Published: January 2013

Membrane proteins regulate vital cellular processes, including signaling, ion transport, and vesicular trafficking. Obtaining experimental access to their structures, conformational fluctuations, orientations, locations, and hydration in membrane environments, as well as the lipid membrane properties, is critical to understanding their functions. Dynamic nuclear polarization (DNP) of frozen solids can dramatically boost the sensitivity of current solid-state nuclear magnetic resonance tools to enhance access to membrane protein structures in native membrane environments. Overhauser DNP in the solution state can map out the local and site-specific hydration dynamics landscape of membrane proteins and lipid membranes, critically complementing the structural and dynamics information obtained by electron paramagnetic resonance spectroscopy. Here, we provide an overview of how DNP methods in solids and solutions can significantly increase our understanding of membrane protein structures, dynamics, functions, and hydration in complex biological membrane environments.
Molecular Switches and Motors on Surfaces
Authors: Pathem Bala Krishna , Claridge Shelley A. , Zheng Yue Bing , Weiss Paul S.
Published: January 2013

Molecular switches and motors respond structurally, electronically, optically, and/or mechanically to external stimuli, testing and potentially enabling extreme miniaturization of optoelectronic devices, nanoelectromechanical systems, and medical devices. The assembly of motors and switches on surfaces makes it possible both to measure the properties of individual molecules as they relate to their environment and to couple function between assembled molecules. In this review, we discuss recent progress in assembling molecular switches and motors on surfaces, measuring static and dynamic structures, understanding switching mechanisms, and constructing functional molecular materials and devices. As demonstrative examples, we choose a representative molecule from three commonly studied classes including molecular switches, photochromic molecules, and mechanically interlocked molecules. We conclude by offering perspectives on the future of molecular switches and motors on surfaces.
Simulation and Theory of Ions at Atmospherically Relevant Aqueous Liquid-Air Interfaces
Authors: Tobias Douglas J. , Stern Abraham C. , Baer Marcel D. , Levin Yan , Mundy Christopher J.
Published: January 2013

Chemistry occurring at or near the surface of aqueous droplets and thin films in the atmosphere influences air quality and climate. Molecular dynamics simulations are becoming increasingly useful for gaining atomic-scale insight into the structure and reactivity of aqueous interfaces in the atmosphere. Here we review simulation studies of atmospherically relevant aqueous liquid-air interfaces, with an emphasis on ions that play important roles in the chemistry of atmospheric aerosols. In addition to surveying results from simulation studies, we discuss challenges to the refinement and experimental validation of the methodology for simulating ion adsorption to the air-water interface and recent advances in elucidating the driving forces for adsorption. We also review the recent development of a dielectric continuum theory capable of reproducing simulation and experimental data on ion behavior at aqueous interfaces.
Peptide-Polymer Conjugates: From Fundamental Science to Application
Authors: Shu Jessica Y. , Panganiban Brian , Xu Ting
Published: January 2013

Peptide/protein-polymer conjugates make up a new class of soft matter comprising natural and synthetic building blocks. They have the potential to combine the advantages of proteins and synthetic polymers (i.e., the precise chemical structure and diverse functionalities of biomolecules and the stability and processability of synthetic polymers) to generate hybrid materials with properties yet to be realized with either component alone. Here we briefly discuss recent developments in the design, fundamental understanding, and self-assembly of various peptide-polymer conjugates, as well as emerging biological and nonbiological applications that range from nanomedicine, to separation, and beyond.