bluuebunny/crossref_metadata_2025 huggingface dataset:
The unhappily unemployed return to work faster
Authors: Mavridis Dimitris
Published: January 2015

This paper shows that job loss is associated with a fall in subjective well-being (SWB). It then looks at how this change in SWB predicts job search and unemployment duration. The findings suggest that those who report feeling hurt by unemployment have shorter unemployment durations. Men who report a loss of SWB are also more likely to look for a job, but women’s job search is not affected by the SWB loss. These findings confirm the theoretical prediction from job search theory: search effort and unemployment duration are affected by the utility differential between having a job and being unemployed.

JEL codes: J64; J28
Effect of peptide length on the conjugation to the gold nanoparticle surface: a molecular dynamic study
Authors: Ramezani Fatemeh , Habibi Mostafa , Rafii-Tabar Hashem , Amanlou Massoud
Published: January 2015

Background

Gold nanoparticles now command a great deal of attention for medical applications. Despite the importance of nano-bio interfaces, interaction between peptides and proteins with gold surfaces is not still fully understood, especially in a molecular level.

Methods

In the present study computational simulation of adsorption of 20 amino acids, in three forms of mono-amino acid, homo di-peptide and homo tri-peptide, on the gold nanoparticles was performed by Gromacs using OPLSAA force field. The flexibility, stability, and size effect of the peptides on the gold nanoparticles were studied as well as the molecular structure of them.

Results

According to our results, adsorbed homo tri-peptides on the gold surface had more flexibility, more gyration, and the farthest distance from the GNP in comparison with homo di-peptides and mono-amino acids.

Conclusion

Our findings provide new insights into the precise control of interactions between amino acids anchored on the GNPs.
Urinary Monocyte Chemoattractant Protein-1 Levels and Interstitial Changes in the Renal Cortex and Their Relationship with Loss of Renal Function in Renal Transplant Patients with Delayed Graft Function
Authors: Neto Miguel Moyses , Romão Elen A , Silva Gyl EB , Dantas Marcio , Nardim Maria EP , Tucci Sylvio , Francescato Heloísa DC , Coimbra Terezila M
Published: January 2015

Background:

Inflammatory cell infiltration and residual areas of fibrosis in kidneys after renal transplantation can lead to functional abnormalities with long-term implications.

Objectives:

The aim of this study was to determine urinary monocyte chemoattractant protein-1 (uMCP-1) levels, relative cortical interstitial area (RCIA), and cortical tubulointerstitial macrophage infiltration in renal transplant patients with delayed graft function (DGF) and their possible correlation with graft outcome.

Design:

Patients were followed after biopsies for one year, and their renal function and structure were evaluated, as well as parameters of inflammatory process.

Setting:

Clinical Hospital of the School of Medicine of Ribeirão Preto.

Patients:

Twenty-two cadaveric kidney transplant recipients with DGF were followed for one year.

Measurements:

Renal function, RCIA, macrophages infiltration and uMCP-1 levels were evaluated.

Methods:

Renal function was evaluated by plasma creatinine levels. RCIA was determined by morphometry. Immunohistochemical staining of macrophages was performed using an anti-CD68 monoclonal antibody. uMCP-1 levels were determined using a human MCP-1/CCL2 immunoassay kit.

Results:

There was a significant increase in uMCP-1 levels in transplant patients compared with controls ( p < 0.001). RCIA was 7.1% (6.4 to 9.2; median and 25th to 75th percentiles) in controls and 37.1% (28.1 to 43.7) in patients with kidney transplants ( p < 0.001). The patients who presented with a higher RCIA in the first biopsy showed higher levels of plasma creatinine one year after transplantation (r = 0.44; p < 0.05). The number of tubulointerstitial macrophages per 0.10 mm2 grid field was higher in the renal cortex of transplant patients compared with the controls (19.4 (9.0 to 47.1) vs. 2.5 (1.8 to 3.4), p < 0.001). There was also a positive correlation between the RCIA and the number of tubulointerstitial macrophages in the renal cortex of these patients (r = 0.49; p < 0.001).

Limitations:

The number of patients studied was relatively small and may not be reflecting outcomes over a larger spectrum of kidney cadaveric transplants.

Conclusions:

Our results demonstrate increased levels of uMCP-1 in transplant patients with DGF, in addition to increased tubulointerstitial macrophage infiltration and RCIA, which could predict the outcome of renal function in these patients.
Characterization of Seismic Levee Fragility Using Field Performance Data
Authors: Kwak Dong Youp , Stewart Jonathan P. , Brandenberg Scott J. , Mikami Atsushi
Published: January 2015

We characterize the seismic fragility of levees along the Shinano River system in Japan using field performance data from two M 6.6 shallow crustal earthquakes. Levee damage is quantified based on crack depth, crack width, and crest subsidence for 3,318 levee segments each 50 m long. Variables considered for possible correlation to damage include peak ground velocity ( PGV), geomorphology, groundwater elevation, and levee geometry. Seismic levee fragility is expressed as the probability of exceeding a damage level conditioned on PGV alone and PGV in combination with other predictive variables. The probability of damage (at any level) monotonically increases from effectively zero for PGV < 14 cm/s to approximately 0.5 for PGV ≈ 80 cm/s. Of the additional parameters considered, groundwater elevation relative to the levee base most significantly affects fragility functions, increasing and decreasing failure probabilities (relative to the PGV-only function) for shallow and deep groundwater conditions, respectively.
Regulation of ryanodine receptor RyR2 by protein-protein interactions: prediction of a PKA binding site on the N-terminal domain of RyR2 and its relation to disease causing mutations
Authors: Walpoth Belinda Nazan , Erman Burak
Published: January 2015

Protein-protein interactions are the key processes responsible for signaling and function in complex networks. Determining the correct binding partners and predicting the ligand binding sites in the absence of experimental data require predictive models. Hybrid models that combine quantitative atomistic calculations with statistical thermodynamics formulations are valuable tools for bioinformatics predictions. We present a hybrid prediction and analysis model for determining putative binding partners and interpreting the resulting correlations in the yet functionally uncharacterized interactions of the ryanodine RyR2 N-terminal domain. Using extensive docking calculations and libraries of hexameric peptides generated from regulator proteins of the RyR2 channel, we show that the residues 318-323 of protein kinase A, PKA, have a very high affinity for the N-terminal of RyR2. Using a coarse grained Elastic Net Model, we show that the binding site lies at the end of a pathway of evolutionarily conserved residues in RyR2. The two disease causing mutations are also on this path. The program for the prediction of the energetically responsive residues by the Elastic Net Model is freely available on request from the corresponding author.
Diagnosis and management of the septic, obstructed kidney
Authors: Arneill Matthew , Hennessey Derek , Glackin Anthony
Published: January 2015

The septic obstructed kidney is a urological emergency and, as such, prompt diagnosis and management are critical in achieving good outcomes. This article highlights the presenting features, radiological investigation and surgical management of this condition, and compares the two methods of surgical decompression.
The missing link: hospital discharge letters following acute kidney injury
Authors: Allen Jennifer , Harrison Laura , Bisset Linda
Published: January 2015

Acute kidney injury (AKI) is a common condition that can lead to significant morbidity such as end-stage renal failure. Relevant information and recommended ongoing management should be conveyed to a GP through a timely, coherent discharge letter. This review of discharge summaries assessed the quality of information received by GPs in AKI patients and its impact on AKI management and long-term prognosis.
Recruitment and retention in the renal unit: interviewing applicants
Authors: Ellis Peter , Abbott Jane
Published: January 2015

Once a shortlist of candidates has been agreed, employers usually use an interview to decide which of the potential new employees is most suitable for the role. In the third article in this series, Peter Ellis and Jane Abbott outline the information that needs to be provided by renal nurse managers before the interview, and then explore the interview process itself and the elements that should be considered.
Drugs commonly used for kidney transplantation
Authors: Ashley Caroline
Published: January 2015

Transplantation is the most effective treatment for patients suffering from chronic renal disease. As each person's body is unique, the transplant team will prescribe medications and dosages especially tailored for the patient receiving the new organ, working to maintain a balance between preventing organ rejection and avoiding infection. In this article, Caroline Ashley gives an overview of the drugs most commonly prescribed by the kidney transplant team.
A new focus on ‘British values’
Authors: Parker Phil
Published: January 2015

The government's focus on ‘British values’ means that spiritual, moral, social and cultural education is firmly back on the map. Phil Parker warns against this being a tick-box exercise
Making an impact…
Authors: Harris Russell
Published: January 2015

After his inner city English department achieved above average results, including excellent pupil progress, we asked Russell Harris to reflect on what strategies made the difference
Pupil Premium interventions
Authors: Adams Corinne
Published: January 2015

Deputy headteacher Corinne Adams discusses her school's Pupil Premium work, including some of the specific interventions they have put in place
Taking a risk with technology
Authors: Pittam Nadine
Published: January 2015

In the coming months, Nadine Pittam will be looking at how we might take small risks in our teaching. This, the first article in the series, examines one of the least dependable and therefore most risky tools a teacher has: technology
Natural acetabular orientation in arthritic hips
Authors: Goudie S. T. , Deakin A. H. , Deep K.
Published: January 2015

Objectives

Acetabular component orientation in total hip arthroplasty (THA) influences results. Intra-operatively, the natural arthritic acetabulum is often used as a reference to position the acetabular component. Detailed information regarding its orientation is therefore essential. The aim of this study was to identify the acetabular inclination and anteversion in arthritic hips.

Methods

Acetabular inclination and anteversion in 65 symptomatic arthritic hips requiring THA were measured using a computer navigation system. All patients were Caucasian with primary osteoarthritis (29 men, 36 women). The mean age was 68 years (SD 8). Mean inclination was 50.5° (SD 7.8) in men and 52.1° (SD 6.7) in women. Mean anteversion was 8.3° (SD 8.7) in men and 14.4° (SD 11.6) in women.

Results

The difference between men and women in terms of anteversion was significant (p = 0.022). In 75% of hips, the natural orientation was outside the safe zone described by Lewinnek et al (anteversion 15° ± 10°; inclination 40° ± 10°).

Conclusion

When using the natural acetabular orientation to guide component placement, it is important to be aware of the differences between men and women, and that in up to 75% of hips natural orientation may be out of what many consider to be a safe zone. Cite this article: Bone Joint Res 2015;4:6–10.
From Westminster
Authors: Leahy Patrick
Published: January 2015

The power of EVEL
Mr Slop and the new Bulletin
Authors: Slop
Published: January 2015

In the bleak midwinter, Slop tries to look on the bright side.
Shining a light
Authors: Marx Clare
Published: January 2015

Transparency is the order of the day, with a fresh round of outcomes data and a more open appointment process at the RCS.
Bionics and prosthetics – into the future
Authors: Bryan Jenny
Published: January 2015

Jenny Bryan presents a handy overview of how far we’ve come, and where we’re going.
A crash revision course in empathy
Authors: West Charles
Published: January 2015

A Wessex trainee finds himself being operated on a month before his finals.
Trials of trauma
Authors: Joshi Meera , Lamah Marc , Surrey Kent
Published: January 2015

All is not as it seems in A&E.
“They Carry Their Religion . . . into Every Act of Their Public and Private Lives”: Quaker Consumption of Early Photographic Images in Philadelphia, 1839–1860
Authors: Verplanck Anne
Published: January 2015

Determining whether, or to what degree, there was a Quaker aesthetic in Philadelphia has challenged scholars for more than half a century. Through their material choices, nineteenth-century Friends consciously and unconsciously conveyed information and ideas about their religious beliefs and the extent of their intersection with non-Quakers to friends, family members, business associates, strangers, and the world at large. An analysis of Philadelphia Quakers’ antebellum photographic consumption, including a comparison with non-Quakers’ selections, reveals that although there was a range of choices of attributes in daguerreotypes among Quakers, their portraits fall at the more restrained end of the spectrum. By choosing a gallery, wearing certain clothing, and opting for a daguerreotype of a particular size and elaboration, Friends balanced their own needs with those of their faith and actively participated in the consumer culture of a major metropolitan area. Their choices invite us to look at how people employed material culture—photographic images and clothing here, but also buildings, landscapes, furniture, and everyday items—and put their imprint on the actions of buying, selling, giving, receiving, and using objects and spaces.
Maintaining a Balance of Power: Michilimackinac, the Anishinaabe Odawas, and the Anglo-Indian War of 1763
Authors: McDonnell Michael A.
Published: January 2015

The famous story of the fall of Michilimackinac is now part of the well-known lore of the war called Pontiac’s. Yet few accounts pause long enough to understand the causes, course, and consequences of the Anglo-Indian War from the perspective of the Anishinaabe people who lived there. Read carefully against the long- and short-term context, the seemingly confused and complex course of events at Michilimackinac in the summer of 1763 can be seen as part of a long-running Anishinaabe strategy to maintain independence in the region by ensuring a balance of power—between Europeans and the Anishinaabeg and other Algonquians of the north, but also between those nations and their southern rivals. Thus, events at the straits of Michilimackinac illuminate some similarities to—but also critical differences from—the war farther south. They also shed much-needed light on inter- and intra-Indian relations both at Michilimackinac and across the pays d’en haut as well as on Indian-European relations in the middle decades of the century. Indeed, events at Michilimackinac compel us to reconsider both English and French relations with the Anishinaabeg and even the very nature and extent of European imperialism in the region.
The Decision to Hire German Troops in the War of American Independence: Reactions in Britain and North America, 1774–1776
Authors: Baer Friederike
Published: January 2015

In the 1770s and 1780s as many as 40,000 German soldiers were hired to defend British imperial interests on four continents. The vast majority—at least 30,000—saw service in America. This article focuses on British and American public reactions to the plan in the period between 1774, when rumors about the intended use of foreign troops first emerged, and the summer of 1776, after the first contingents of German troops had arrived in North America but before military encounters with the colonists had taken place. In Britain, the reliance on forces from outside the empire in a conflict believed to be about British liberties provoked strong opposition. Critics used the hire of “barbarians” as evidence of a sinister plot to deprive Englishmen of their liberties. In America, news of the plan to hire Germans gave radicals an effective tool in their efforts to unite the colonists against the British. An analysis of these public debates sheds light on conflicting perceptions of Britishness and “foreignness” during the Revolutionary period.
Crèvecoeur’s Trans-Atlantic Bilingualism
Authors: McMurran Mary Helen
Published: January 2015

Hector St. John de Crèvecoeur’s French version of his Letters from an American Farmer is at once inextricably linked to, but wholly different from, his English manuscripts. This essay proposes that a study of this overlooked bilingual text should begin by forgoing a comparison of the two versions and instead investigate Crèvecoeur’s bilingualism in its eighteenth-century trans-Atlantic context. An account of Crèvecoeur’s bilingual code-switching, his linguistic affect, and his commitment to language acquisition reveals the complex interrelation of languages in his nomadic life. At a time when using more than one language was not anomalous, but in tension with attempts to establish a stable national vernacular, Crèvecoeur’s case also illuminates frictions in the Atlantic’s linguistic ecology. This essay demonstrates that multilingualism and a standardized national language were not competitors, but coexisted in a fragile linguistic habitat.
Modernization of Libraries in a Postcommunist State: The Roles of the George Soros, Andrew W. Mellon, and Bill & Melinda Gates Foundations in the Development of Latvian Libraries
Authors: Vilks Andris , Dreimane Jana
Published: January 2015

This paper presents the most important changes in the library system of Latvia in the late 1980s, when, as a result of a nonviolent struggle, Latvia regained full independence from the Soviet Union in 1990. Particular attention is paid to contributions by private foundations in the United States—the George Soros, Andrew W. Mellon, and Bill & Melinda Gates Foundations—to fulfill the main goal of library work: namely, helping to create a democratic society in which everyone has the opportunity to express their views and be able to freely access information. During the Soviet period, libraries were mainly agents of the dominant power; they were often forced to ignore the needs of Latvian society or even to work against them. The activities of libraries were strictly regulated and controlled. Latvian independence has allowed the libraries to end political censorship and strict control, and to independently determine their future directions and work methods. Political changes occurred so rapidly that the immediate normalization of professional work after fifty years of occupation was not possible. However, US private foundations supported strategically important areas of library work: automation and access to the internet, the creation of the State Unified Library Information System (SULIS), and the professional development of library staff. The US foundations, through requirements for the cofinancing of large-scale projects, also motivated state and municipalities in Latvia to increase their investment in libraries. The interest expressed in libraries by these foundations emphasized that Latvian libraries were vital. Consequently, targeted investments shortly after independence ensured the timely inclusion of the basic elements of the national library system—the National Library of Latvia and public, school, and academic libraries—in the modern information environment, thus allowing them to fulfill the main task of all libraries: the provision of public access to information.
Developing the Library Network in Postcommunist Russia: Trends, Issues, and Perspectives
Authors: Zverevich Victor
Published: January 2015

This paper discusses trends in library network development in Russia over the past twenty-five years. The major trends in libraries of various types and levels, from national to local public libraries, are analyzed. Statistical figures reflecting decreasing numbers of libraries in Russia from 1991 to the present are presented and analyzed. A special section is dedicated to the B. N. Yeltsin Presidential Library in St. Petersburg, the electronic national library of Russia. The public library development strategy in St. Petersburg is highlighted, along with the reform of the network of public libraries in Moscow. The two most recently renovated libraries in Moscow, the F. M. Dostoevsky Library and the Prospekt Library and Information Center, are featured. The major directions for Russian libraries desiring to go “green” are presented, along with the conditions they are to meet.
Libraries and Librarianship in the Republic of Macedonia
Authors: Kostoska Viktorija , Gjalevska Zhaklina , Nikodinovska Elena , Shambevska Magdica , Jakovleska-Spirovska Zorica
Published: January 2015

Libraries and librarianship in the Republic of Macedonia have a tradition spanning centuries, one that is linked to the work of Saint Clement of Ohrid and the first Slavic university in the monasteries on the banks of Lake Ohrid. Libraries and librarianship are the fountain springs of Macedonian culture but also the foundation of its ongoing mission. Libraries in Macedonia are following new trends and tendencies in their efforts to build a national library-information system, with shared cataloging as part of the regional library network (COBISS.net). Building on the continuous application of the traditional types of preservation of library materials along with contemporary methods and technologies, current practice has expanded to include digitalization. This has ensured easy online access to Mace-donia’s rich library holdings, offered opportunities for its written cultural heritage to be presented in both digital and traditional formats, and opened up new paths for greater international cooperation.
Money, Time, and the Stability of Consumer Preferences
Authors: Lee Leonard , Lee Michelle P. , Bertini Marco , Zauberman Gal , Ariely Dan
Published: January 2015

Consumers often make product choices that involve the consideration of money and time. Building on dual-process models, the authors propose that these two basic resources activate qualitatively different modes of processing: while money is processed analytically, time is processed more affectively. Importantly, this distinction then influences the stability of consumer preferences. An initial set of three experiments demonstrates that, compared with a control condition free of the consideration of either resource, money consideration generates significantly more violations of transitivity in product choice, while time consideration has no such impact. The next three experiments use multiple approaches to demonstrate the role of different processing modes associated with money versus time consideration in this result. Finally, two additional experiments test ways in which the cognitive noise associated with the analytical processing that money consideration triggers could be reduced, resulting in more consistent preferences.
Constitutional Design and 2014 Senate Election Outcomes
Authors: Highton Benjamin , McGhee Eric , Sides John
Published: January 2015

A common observation about the 2014 Senate elections is that one advantage the Republicans had was that the set of states holding elections tilted Republican in partisanship. In this article, we quantify that advantage and demonstrate that the constitutional requirements of equality for state representation in the Senate plus the division of seats into three classes were critical elements in the Republicans’ pickup of nine seats and retaking partisan control. Markedly less important was the national Republican partisan tide.
Preference Dynamics in the 2014 Congressional Midterm Elections
Authors: Panagopoulos Costas
Published: January 2015

The vote intentions of Americans experienced meaningful change over the course of the 2014 campaign, largely to the detriment of Democrats and in favor of the GOP. Vote intention trajectories generally followed sensible and predictable patterns, reflecting forces and developments that unfolded over the course of the campaign cycle. Specifically, changes in voter sentiments were fueled primarily by assessments about the president and, relatedly, about the condition of the national economy. Higher levels of Obama approval helped Democratic contenders over the course of the 2014 midterm cycle, while Republicans appeared to benefit from improvements in the economy. Political events and assessments of congressional performance were unrelated to vote intentions in 2014.
A universal mechanism for transport and regulation of CPA sodium proton exchangers
Authors: Călinescu Octavian , Fendler Klaus
Published: January 2015

Recent studies performed on a series of Na+/H+ exchangers have led us to postulate a general mechanism for Na+/H+ exchange in the monovalent cation/proton antiporter superfamily. This simple mechanism employs a single binding site for which both substrates compete. The developed kinetic model is self-regulatory, ensuring down-regulation of transport activity at extreme pH, and elegantly explains the pH-dependent activity of Na+/H+ exchangers. The mechanism was experimentally verified and shown to describe both electrogenic and electroneutral exchangers. Using a small number of parameters, exchanger activity can be modeled under different conditions, providing insights into the physiological role of Na+/H+ exchangers.
Interesting properties of p-, d-, and f-block elements when coordinated with dipicolinic acid and its derivatives as ligands: their use as inorganic pharmaceuticals
Authors: Celestine Michael J. , Bullock Jimmie L. , Boodram Shivani , Rambaran Varma H. , Holder Alvin A.
Published: January 2015

This is a review of the literature concerning the interesting properties of p-, d-, and f-block elements when coordinated with 2,6-pyridinedicarboxylic acid (dipicolinic acid, H2 dipic) and its derivatives as ligands, with a focus on their use as inorganic pharmaceuticals. Some of the complexes reported were used as insulin-like, bioimaging contrasting agents, antimicrobial agents, and anticancer agents.
Left Dorsal Speech Stream Components and Their Contribution to Phonological Processing
Authors: Murakami Takenobu , Kell Christian A. , Restle Julia , Ugawa Yoshikazu , Ziemann Ulf
Published: January 2015

Models propose an auditory-motor mapping via a left-hemispheric dorsal speech-processing stream, yet its detailed contributions to speech perception and production are unclear. Using fMRI-navigated repetitive transcranial magnetic stimulation (rTMS), we virtually lesioned left dorsal stream components in healthy human subjects and probed the consequences on speech-related facilitation of articulatory motor cortex (M1) excitability, as indexed by increases in motor-evoked potential (MEP) amplitude of a lip muscle, and on speech processing performance in phonological tests. Speech-related MEP facilitation was disrupted by rTMS of the posterior superior temporal sulcus (pSTS), the sylvian parieto-temporal region (SPT), and by double-knock-out but not individual lesioning of pars opercularis of the inferior frontal gyrus (pIFG) and the dorsal premotor cortex (dPMC), and not by rTMS of the ventral speech-processing stream or an occipital control site. RTMS of the dorsal stream but not of the ventral stream or the occipital control site caused deficits specifically in the processing of fast transients of the acoustic speech signal. Performance of syllable and pseudoword repetition correlated with speech-related MEP facilitation, and this relation was abolished with rTMS of pSTS, SPT, and pIFG. Findings provide direct evidence that auditory-motor mapping in the left dorsal stream causes reliable and specific speech-related MEP facilitation in left articulatory M1. The left dorsal stream targets the articulatory M1 through pSTS and SPT constituting essential posterior input regions and parallel via frontal pathways through pIFG and dPMC. Finally, engagement of the left dorsal stream is necessary for processing of fast transients in the auditory signal.
Opioid Receptor-Dependent Sex Differences in Synaptic Plasticity in the Hippocampal Mossy Fiber Pathway of the Adult Rat
Authors: Harte-Hargrove Lauren C. , Varga-Wesson Ada , Duffy Aine M. , Milner Teresa A. , Scharfman Helen E.
Published: January 2015

The mossy fiber (MF) pathway is critical to hippocampal function and influenced by gonadal hormones. Physiological data are limited, so we asked whether basal transmission and long-term potentiation (LTP) differed in slices of adult male and female rats. The results showed small sex differences in basal transmission but striking sex differences in opioid receptor sensitivity and LTP. When slices were made from females on proestrous morning, when serum levels of 17β-estradiol peak, the nonspecific opioid receptor antagonist naloxone (1 μm) enhanced MF transmission but there was no effect in males, suggesting preferential opioid receptor-dependent inhibition in females when 17β-estradiol levels are elevated. The μ-opioid receptor (MOR) antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP; 300 nm) had a similar effect but the δ-opioid receptor (DOR) antagonist naltrindole (NTI; 1 μm) did not, implicating MORs in female MF transmission. The GABABreceptor antagonist saclofen (200 μm) occluded effects of CTOP but the GABAAreceptor antagonist bicuculline (10 μm) did not. For LTP, a low-frequency (LF) protocol was used because higher frequencies elicited hyperexcitability in females. Proestrous females exhibited LF-LTP but males did not, suggesting a lower threshold for synaptic plasticity when 17β-estradiol is elevated. NTI blocked LF-LTP in proestrous females, but CTOP did not. Electron microscopy revealed more DOR-labeled spines of pyramidal cells in proestrous females than males. Therefore, we suggest that increased postsynaptic DORs mediate LF-LTP in proestrous females. The results show strong MOR regulation of MF transmission only in females and identify a novel DOR-dependent form of MF LTP specific to proestrus.
Plasticity during Motherhood: Changes in Excitatory and Inhibitory Layer 2/3 Neurons in Auditory Cortex
Authors: Cohen Lior , Mizrahi Adi
Published: January 2015

Maternal behavior can be triggered by auditory and olfactory cues originating from the newborn. Here we report how the transition to motherhood affects excitatory and inhibitory neurons in layer 2/3 (L2/3) of the mouse primary auditory cortex. We usedin vivotwo-photon targeted cell-attached recording to compare the response properties of parvalbumin-expressing neurons (PVNs) and pyramidal glutamatergic neurons (PyrNs). The transition to motherhood shifts the average best frequency of PVNs to higher frequency by a full octave, with no significant effect on average best frequency of PyrNs. The presence of pup odors significantly reduced the spontaneous and evoked activity of PVN. This reduction of feedforward inhibition coincides with a complimentary increase in spontaneous and evoked activity of PyrNs. The selective shift of PVN frequency tuning should render pup odor-induced disinhibition more effective for high-frequency stimuli, such as ultrasonic vocalizations. Indeed, pup odors increased neuronal responses of PyrNs to pup ultrasonic vocalizations. We conclude that plasticity in the mothers is mediated, at least in part, via modulation of the feedforward inhibition circuitry in the auditory cortex.
Action and Perception Are Temporally Coupled by a Common Mechanism That Leads to a Timing Misperception
Authors: Pretegiani Elena , Astefanoaei Corina , Daye Pierre M. , FitzGibbon Edmond J. , Creanga Dorina-Emilia , Rufa Alessandra , Optican Lance M.
Published: January 2015

We move our eyes to explore the world, but visual areas determining where to look next (action) are different from those determining what we are seeing (perception). Whether, or how, action and perception are temporally coordinated is not known. The preparation time course of an action (e.g., a saccade) has been widely studied with the gap/overlap paradigm with temporal asynchronies (TA) between peripheral target onset and fixation point offset (gap, synchronous, or overlap). However, whether the subjects perceive the gap or overlap, and when they perceive it, has not been studied. We adapted the gap/overlap paradigm to study the temporal coupling of action and perception. Human subjects made saccades to targets with different TAs with respect to fixation point offset and reported whether they perceived the stimuli as separated by a gap or overlapped in time. Both saccadic and perceptual report reaction times changed in the same way as a function of TA. The TA dependencies of the time change for action and perception were very similar, suggesting a common neural substrate. Unexpectedly, in the perceptual task, subjects misperceived lights overlapping by less than ∼100 ms as separated in time (overlap seen as gap). We present an attention-perception model with a map of prominence in the superior colliculus that modulates the stimulus signal's effectiveness in the action and perception pathways. This common source of modulation determines how competition between stimuli is resolved, causes the TA dependence of action and perception to be the same, and causes the misperception.
Lymphocytes from Chronically Stressed Mice Confer Antidepressant-Like Effects to Naive Mice
Authors: Brachman Rebecca A. , Lehmann Michael L. , Maric Dragan , Herkenham Miles
Published: January 2015

We examined whether cells of the adaptive immune system retain the memory of psychosocial stress and thereby alter mood states and CNS function in the host. Lymphocytes from mice undergoing chronic social defeat stress or from unstressed control mice were isolated and adoptively transferred into naive lymphopenic Rag2−/−mice. Changes in affective behavior, hippocampal cell proliferation, microglial activation states, and blood cytokine levels were examined in reconstituted stress-naive mice. The mice receiving lymphocytes from defeated donors showed less anxiety, more social behavior, and increased hippocampal cell proliferation compared with those receiving no cells or cells from unstressed donors. Mice receiving stressed immune cells had reduced pro-inflammatory cytokine levels in the blood relative to the other groups, an effect opposite to the elevated donor pro-inflammatory cytokine profile. Furthermore, mice receiving stressed immune cells had microglia skewed toward an anti-inflammatory, neuroprotective M2-like phenotype, an effect opposite the stressed donors' M1-like pro-inflammatory profile. However, stress had no effect on lymphocyte surface marker profiles in both donor and recipient mice. The data suggest that chronic stress-induced changes in the adaptive immune system, contrary to conferring anxiety and depressive behavior, protect against the deleterious effects of stress. Improvement in affective behavior is potentially mediated by reduced peripheral pro-inflammatory cytokine load, protective microglial activity, and increased hippocampal cell proliferation. The data identify the peripheral adaptive immune system as putatively involved in the mechanisms underlying stress resilience and a potential basis for developing novel rapid-acting antidepressant therapies.
Mechanism of Neuromuscular Dysfunction in Krabbe Disease
Authors: Cantuti-Castelvetri Ludovico , Maravilla Erick , Marshall Michael , Tamayo Tammy , D'auria Ludovic , Monge John , Jeffries James , Sural-Fehr Tuba , Lopez-Rosas Aurora , Li Guannan , Garcia Kelly , van Breemen Richard , Vite Charles , Garcia Jesus , Bongarzone Ernesto R.
Published: January 2015

The atrophy of skeletal muscles in patients with Krabbe disease is a major debilitating manifestation that worsens their quality of life and limits the clinical efficacy of current therapies. The pathogenic mechanism triggering muscle wasting is unknown. This study examined structural, functional, and metabolic changes conducive to muscle degeneration in Krabbe disease using the murine (twitcher mouse) and canine [globoid cell leukodystrophy (GLD) dog] models. Muscle degeneration, denervation, neuromuscular [neuromuscular junction (NMJ)] abnormalities, and axonal death were investigated using the reporter transgenic twitcher–Thy1.1–yellow fluorescent protein mouse. We found that mutant muscles had significant numbers of smaller-sized muscle fibers, without signs of regeneration. Muscle growth was slow and weak in twitcher mice, with decreased maximum force. The NMJ had significant levels of activated caspase-3 but limited denervation. Mutant NMJ showed reduced surface areas and lower volumes of presynaptic terminals, with depressed nerve control, increased miniature endplate potential (MEPP) amplitude, decreased MEPP frequency, and increased rise and decay rate constants. Twitcher and GLD dog muscles had significant capacity to store psychosine, the neurotoxin that accumulates in Krabbe disease. Mechanistically, muscle defects involved the inactivation of the Akt pathway and activation of the proteasome pathway. Our work indicates that muscular dysfunction in Krabbe disease is compounded by a pathogenic mechanism involving at least the failure of NMJ function, activation of proteosome degradation, and a reduction of the Akt pathway. Akt, which is key for muscle function, may constitute a novel target to complement in therapies for Krabbe disease.
Neural Mechanisms for Integrating Prior Knowledge and Likelihood in Value-Based Probabilistic Inference
Authors: Ting Chih-Chung , Yu Chia-Chen , Maloney Laurence T. , Wu Shih-Wei
Published: January 2015

In Bayesian decision theory, knowledge about the probabilities of possible outcomes is captured by a prior distribution and a likelihood function. The prior reflects past knowledge and the likelihood summarizes current sensory information. The two combined (integrated) form a posterior distribution that allows estimation of the probability of different possible outcomes. In this study, we investigated the neural mechanisms underlying Bayesian integration using a novel lottery decision task in which both prior knowledge and likelihood information about reward probability were systematically manipulated on a trial-by-trial basis. Consistent with Bayesian integration, as sample size increased, subjects tended to weigh likelihood information more compared with prior information. Using fMRI in humans, we found that the medial prefrontal cortex (mPFC) correlated with the mean of the posterior distribution, a statistic that reflects the integration of prior knowledge and likelihood of reward probability. Subsequent analysis revealed that both prior and likelihood information were represented in mPFC and that the neural representations of prior and likelihood in mPFC reflected changes in the behaviorally estimated weights assigned to these different sources of information in response to changes in the environment. Together, these results establish the role of mPFC in prior-likelihood integration and highlight its involvement in representing and integrating these distinct sources of information.
An Acto-Myosin II Constricting Ring Initiates the Fission of Activity-Dependent Bulk Endosomes in Neurosecretory Cells
Authors: Gormal Rachel S. , Nguyen Tam H. , Martin Sally , Papadopulos Andreas , Meunier Frederic A.
Published: January 2015

Activity-dependent bulk endocytosis allows neurons to internalize large portions of the plasma membrane in response to stimulation. However, whether this critical type of compensatory endocytosis is unique to neurons or also occurs in other excitable cells is currently unknown. Here we used fluorescent 70 kDa dextran to demonstrate that secretagogue-induced bulk endocytosis also occurs in bovine chromaffin cells. The relatively large size of the bulk endosomes found in this model allowed us to investigate how the neck of the budding endosomes constricts to allow efficient recruitment of the fission machinery. Using time-lapse imaging of Lifeact–GFP-transfected chromaffin cells in combination with fluorescent 70 kDa dextran, we detected acto-myosin II rings surrounding dextran-positive budding endosomes. Importantly, these rings were transient and contracted before disappearing, suggesting that they might be involved in restricting the size of the budding endosome neck. Based on the complete recovery of dextran fluorescence after photobleaching, we demonstrated that the actin ring-associated budding endosomes were still connected with the extracellular fluid. In contrast, no such recovery was observed following the constriction and disappearance of the actin rings, suggesting that these structures were pinched-off endosomes. Finally, we showed that the rings were initiated by a circular array of phosphatidylinositol(4,5)bisphosphate microdomains, and that their constriction was sensitive to both myosin II and dynamin inhibition. The acto-myosin II rings therefore play a key role in constricting the neck of budding bulk endosomes before dynamin-dependent fission from the plasma membrane of neurosecretory cells.
Elucidating the Role of AII Amacrine Cells in Glutamatergic Retinal Waves
Authors: Firl Alana , Ke Jiang-Bin , Zhang Lei , Fuerst Peter G. , Singer Joshua H. , Feller Marla B.
Published: January 2015

Spontaneous retinal activity mediated by glutamatergic neurotransmission—so-called “Stage 3” retinal waves—drives anti-correlated spiking in ON and OFF RGCs during the second week of postnatal development of the mouse. In the mature retina, the activity of a retinal interneuron called the AII amacrine cell is responsible for anti-correlated spiking in ON and OFF α-RGCs. In mature AIIs, membrane hyperpolarization elicits bursting behavior. Here, we postulated that bursting in AIIs underlies the initiation of glutamatergic retinal waves. We tested this hypothesis by using two-photon calcium imaging of spontaneous activity in populations of retinal neurons and by making whole-cell recordings from individual AIIs and α-RGCs inin vitropreparations of mouse retina. We found that AIIs participated in retinal waves, and that their activity was correlated with that of ON α-RGCs and anti-correlated with that of OFF α-RGCs. Though immature AIIs lacked the complement of membrane conductances necessary to generate bursting, pharmacological activation of the M-current, a conductance that modulates bursting in mature AIIs, blocked retinal wave generation. Interestingly, blockade of the pacemaker conductanceIh, a conductance absent in AIIs but present in both ON and OFF cone bipolar cells, caused a dramatic loss of spatial coherence of spontaneous activity. We conclude that during glutamatergic waves, AIIs act to coordinate and propagate activity generated by BCs rather than to initiate spontaneous activity.
Plasticity of Intact Rubral Projections Mediates Spontaneous Recovery of Function after Corticospinal Tract Injury
Authors: Siegel Chad S. , Fink Kathren L. , Strittmatter Stephen M. , Cafferty William B.J.
Published: January 2015

Axons in the adult CNS fail to regenerate after injury, and therefore recovery from spinal cord injury (SCI) is limited. Although full recovery is rare, a modest degree of spontaneous recovery is observed consistently in a broad range of clinical and nonclinical situations. To define the mechanisms mediating spontaneous recovery of function after incomplete SCI, we created bilaterally complete medullary corticospinal tract lesions in adult mice, eliminating a crucial pathway for voluntary skilled movement. Anatomic and pharmacogenetic tools were used to identify the pathways driving spontaneous functional recovery in wild-type and plasticity-sensitized mice lacking Nogo receptor 1. We found that plasticity-sensitized mice recovered 50% of normal skilled locomotor function within 5 weeks of lesion. This significant, yet incomplete, spontaneous recovery was accompanied by extensive sprouting of intact rubrofugal and rubrospinal projections with the emergence of ade novocircuit between the red nucleus and the nucleus raphe magnus. Transient silencing of this rubro–raphe circuitin vivovia activation of the inhibitory DREADD (designer receptor exclusively activated by designer drugs) receptor hM4di abrogated spontaneous functional recovery. These data highlight the pivotal role of uninjured motor circuit plasticity in supporting functional recovery after trauma, and support a focus of experimental strategies on enhancing intact circuit rearrangement to promote functional recovery after SCI.
High revivability of vitrified–warmed bovine mature oocytes after recovery culture with α-tocopherol
Authors: Yashiro Ikuko , Tagiri Miho , Ogawa Hayato , Tashima Kazuya , Takashima Seiji , Hara Hiromasa , Hirabayashi Masumi , Hochi Shinichi
Published: January 2015

The objective of this study was to investigate whether developmental competence of vitrified–warmed bovine oocytes can be improved by antioxidant treatment during recovery culture. In experiment 1, one of the two antioxidants (either l-ascorbic acid or α-tocopherol) was added as a supplement to the recovery culture medium to which postwarming oocytes were exposed for 2 h before IVF. The exposure to α-tocopherol had a positive effect on rescuing the oocytes as assessed by the blastocyst yield 8 days after the IVF (35.1–36.3% vs 19.2–25.8% in untreated postwarming oocytes). Quality of expanding blastocysts harvested on Day 8 was comparable between α-tocopherol-treated vitrification group and fresh control group in terms of total cell number and chromosomal ploidy. In experiment 2, level of reactive oxygen species, mitochondrial activity, and distribution of cortical granules in α-tocopherol-treated postwarming oocytes were assessed. No obvious differences from the control data were found in these parameters. However, the treatment with α-tocopherol increased the percentage of zygotes exhibiting normal single aster formation (90.3% vs 48.0% in untreated postwarming oocytes; 10 h post-IVF). It was concluded that α-tocopherol treatment of vitrified–warmed bovine mature oocytes during recovery culture can improve their revivability, as shown by the high blastocyst yield and the higher mean total cell number in the blastocysts.
On the role of germ cells in mammalian gonad development: quiet passengers or back-seat drivers?
Authors: Rios-Rojas Clarissa , Bowles Josephine , Koopman Peter
Published: January 2015

In addition to their role as endocrine organs, the gonads nurture and protect germ cells, and regulate the formation of gametes competent to convey the genome to the following generation. After sex determination, gonadal somatic cells use several known signalling pathways to direct germ cell development. However, the extent to which germ cells communicate back to the soma, the molecular signals they use to do so and the significance of any such signalling remain as open questions. Herein, we review findings arising from the study of gonadal development and function in the absence of germ cells in a range of organisms. Most published studies support the view that germ cells are unimportant for foetal gonadal development in mammals, but later become critical for stabilisation of gonadal function and somatic cell phenotype. However, the lack of consistency in the data, and clear differences between mammals and other vertebrates and invertebrates, suggests that the story may not be so simple and would benefit from more careful analysis using contemporary molecular, cell biology and imaging tools.