bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer and life-history traits: lessons from host–parasite interactions
Authors: UJVARI BEATA , BECKMANN CHRISTA , BIRO PETER A. , ARNAL AUDREY , TASIEMSKI AURELIE , MASSOL FRANCOIS , SALZET MICHEL , MERY FREDERIC , BOIDIN-WICHLACZ CELINE , MISSE DOROTHEE , RENAUD FRANCOIS , VITTECOQ MARION , TISSOT TAZZIO , ROCHE BENJAMIN , POULIN ROBERT , THOMAS FREDERIC
Published: February 2016

Despite important differences between infectious diseases and cancers, tumour development (neoplasia) can nonetheless be closely compared to infectious disease because of the similarity of their effects on the body. On this basis, we predict that many of the life-history (LH) responses observed in the context of host–parasite interactions should also be relevant in the context of cancer. Parasites are thought to affect LH traits of their hosts because of strong selective pressures like direct and indirect mortality effects favouring, for example, early maturation and reproduction. Cancer can similarly also affect LH traits by imposing direct costs and/or indirectly by triggering plastic adjustments and evolutionary responses. Here, we discuss how and why a LH focus is a potentially productive but under-exploited research direction for cancer research, by focusing our attention on similarities between infectious disease and cancer with respect to their effects on LH traits and their evolution. We raise the possibility that LH adjustments can occur in response to cancer via maternal/paternal effects and that these changes can be heritable to (adaptively) modify the LH traits of their offspring. We conclude that LH adjustments can potentially influence the transgenerational persistence of inherited oncogenic mutations in populations.
The Proto-Indoaryans
Authors: Burrow T.
Published: February 2016

It is now generally agreed by most authorities on the subject that the Aryan linguistic vestiges in the Near East are to be connected specifically with Indo-Aryan, and not with Iranian, and also that they do not represent a third, independent Aryan group, and are not to be ascribed to the hypothetically reconstructed Proto-Aryan. This conclusion is incorporated in the title of M. Mayrhofer's bibliography of the subject,Die Indo-Arier im alten Vorderasien(Wiesbaden, 1966), and it can now be taken as the commonly accepted view. It is based on the fact that where there is divergence between Iranian and Indo-Aryan, and where such elements appear in the Near Eastern record, the latter always agrees with Indo-Aryan. Such items areaika“one” andšuriyaš“sun”, and the colour namesparita-nnuandpinkara-nnuwhich correspond to Sanskritpalita- “grey” andpiṅgala- “reddish”. The evidence of vocabulary is supported by that of the four names of gods appearing in the Hittite-Mitanni treaty, where the Vedic gods Mitra and Varuṇa, Indra, and the Nāsatyas can be clearly recognized. This combined evidence is sufficient to establish the conclusions of Mayrhofer and others beyond reasonable doubt, and the arguments of A. Kammenhuber, who later attempted to resuscitate the theory that the Aryans of the Near East were Proto-Aryans, cannot be said to have been successful.
Mirror neurons: A sensorimotor representation system
Authors: Gallese Vittorio , Keysers Christian
Published: February 2016

Positing the importance of sensorimotor contingencies for perception is by no means denying the presence and importance of representations. Using the evidence of mirror neurons we will show the intrinsic relationship between action control and representation within the logic of forward models.
A numerical study of ponderomotive ion acceleration in a dense plasma driven by a circularly polarized high-intensity laser beam normally incident on thin foils
Authors: Shoucri Magdi , Vidal François , Matte Jean-Pierre
Published: February 2016

We use an Eulerian Vlasov code to study the efficient ion acceleration in dense targets by the ponderomotive force of a high-intensity circularly polarized laser beam, normally incident on a dense plasma. The code solves the one-dimensional relativistic Vlasov–Maxwell equations for both electrons and ions. We follow in details the mechanism of formation and evolution of a double-layer structure, where electrons are pushed steadily in the forward direction by the ponderomotive force of the laser beam, trapping an ion population, while an induced space charge electric field pulls ions behind them, forming a double-layer structure supported by the strong ponderomotive pressure of the intense laser beam. We consider the case of a high-density deuterium plasma with n/ncr = 100, where ncr is the critical density. Three cases are studied, by varying the width of the dense target and the intensity of the laser beam (with the normalized vector potential or quiver momentum a0 = 50 and a0 = 100), to follow the physical processes involved in the ion acceleration and the final formation of a neutral plasma jet ejected from the back of the target. We follow the transition from a situation where the laser pulse radiation pressure is acting on the double layer in the target, to a situation where below a given thickness a fraction of the laser energy is transmitted through the target. The absence of noise in the Eulerian Vlasov code allows us to follow accurately the evolution of the phase-space structures of the distribution functions.
Study of crossed-beam energy transfer process with large crossing angle in three-dimension
Authors: Hao L. , Hu X. Y. , Zheng C. Y. , Li B. , Xiang J. , Liu Z. J.
Published: February 2016

In this paper, a three-dimensional (3D) model as a new module of LAP3D code is presented to study the crossed-beam energy transfer (CBET) process. This model is not limited by the paraxial approximation and can be used to deal with a large crossing angle case. Besides, this model is also appropriate for the multi-ion species conditions and even multi-beams problems, which will be very helpful in relevant experiment analysis and the target design. In our 3D simulations, we take the overlapped beams with a 60° crossing angle as an example, and observe obvious energy transfer process, which indicates CBET process might occur between the incident laser beams with a large crossing angle when the matching condition is satisfied. This large crossing angle CBET process also can change the spatial shape of the beam spot, and may have some potential important influence on other laser–plasma interaction instabilities and the energy symmetry in hohlraum.
Consciousness and Cell Memory: A Dynamic Epigenetic Interrelationship
Authors: Hudson Arthur J.
Published: February 2016

There have been great advances in the neurological sciences in recent years including some in the higher functions of the brain such as memory but one of the more critical of these with close ties to memory is consciousness which remains an enigma. Revolutionary developments in genetics during the last two decades, referred to as epigenetics, have provided opportunity for discovery. The chromatin in the cell nucleus consists mainly of DNA nucleotides and histone proteins and the DNA is dynamically and epigenetically altered by the local actions of enzymes and trans-acting factors on the adjacent histone amino acids. DNA is also directly activated or inhibited by methyl groups and by non-coding RNAs. Epigenetics is a determinant in long-term cell memory consolidation and, as recently demonstrated in animal and human studies and described here, these effects enable a rapid and extraordinarily complex cognitive matching of cell memory to experience during consciousness.
Rabies in the Critical Care Unit: Diagnostic and Therapeutic Approaches
Authors: Jackson Alan C.
Published: February 2016

Worldwide, human rabies is prevalent where there is endemic dog rabies, but the disease may present unexpectedly in critical care units when suggestive clinical features have passed. In North America transmission from bats is most common and there is often no history of a bat bite or even contact with bats. Laboratory diagnostic evaluation for rabies includes serology plus skin biopsy, cerebrospinal fluid, and saliva specimens for rabies virus antigen and/or RNA detection. Rare patients have survived rabies, and most received rabies vaccine prior to the onset of illness. Therapeutic coma (midazolam and phenobarbital), ketamine, and antiviral therapies (dubbed the "Milwaukee Protocol") were given to a rabies survivor, but this therapy was likely not directly responsible for the favorable outcome. There have been many subsequent failures of similar therapeutic approaches. There is no scientific rationale for the use of therapeutic coma in human rabies. New approaches to treating human rabies need to be developed.
Impact of the Cognitive Status on the Memory Complaints in MS Patients
Authors: Demers M. , Rouleau I. , Scherze P. , Ouellet J. , Jobin C. , Duquette P.
Published: February 2016

Objective:

Despite the evidence of cognitive deficits in Multiple Sclerosis (MS) patients, evaluation of their cognitive integrity is often limited to the use of clinical interviews and questionnaires. However, the consensus in the literature is that these patients under- or overestimate their deficits and repercussions. The objective of this study was to clarify why some patients overestimate while others underestimate their memory deficits.

Method:

Fifty-four participants (30 MS, 24 controls) completed the Prospective and Retrospective Memory Questionnaire (PRMQ) and were tested on a battery of neuropsychological tests. Based on the test results, MS patients were categorized as having either mild or moderate/severe cognitive deficits.

Results:

The moderate/severe MS group differed from the two other groups on the Rey Auditory Verbal Learning Test (RAVLT) but did not differ from the control group on the PRMQ. Conversely, the mild MS group did not differ from the control group on the RAVLT but did report significantly more problems than this group on the PRMQ. There was no difference between the two clinical groups on the Depression Index (Beck) but there was a significant correlation (r=.409) between the depression scores and the overestimation of prospective memory problems (PRMQ).

Conclusion:

The results explain the contradiction in the literature. It is the mild group who overestimates, maybe because they are overly concerned by their deficits, whereas the cognitive impairments of the moderate/severe group lead them to underestimate and may make their self-assessment unreliable. Formal testing or information from a significant other would be advisable.
Complications in MS Patients after CCSVI Procedures Abroad (Calgary, AB)
Authors: Burton Jodie M. , Alikhani Katayoun , Goyal Mayank , Costello Fiona , White Chris , Patry David , Bell Robert , Hill Michael D.
Published: February 2016

Background:

The “chronic cerebrospinal venous insufficiency” or “CCSVI” hypothesis, namely that multiple sclerosis (MS) is caused by abnormalities in the azygous and internal jugular veins with subsequent alterations in venous hemodynamics in the central nervous system, has been a dominant topic in MS care in Canada over the past year. Although there is no methodologically rigorous evidence to support this hypothesis presently, a considerable number of MS patients have undergone endovascular CCSVI procedures. Such procedures include angioplasty or stent placement in jugular and azygous veins. The safety and efficacy of these procedures is unknown, but not without risk.

Methods:

Chart and patient review of five patients with confirmed MS followed in Calgary were undertaken after patients came to medical attention by referral or admission secondary to complications believed to be associated with CCSVI procedures.

Results:

Complications upon investigation and review included internal jugular vein stent thrombosis, cerebral sinovenous thrombosis, stent migration, cranial nerve injury and injury associated with venous catheterization.

Conclusions:

As the debate about CCSVI and its relationship to MS continues, the complications and risks associated with venous stenting and angioplasty in jugular and azygous veins are becoming clearer. As increasing numbers of MS patients are seeking such procedures, these five cases represent the beginning of a wave of complications for which standardized care guidelines do not exist. Our experience and that of our colleagues will be used to develop guidelines and strategies to monitor and manage these patients as their numbers increase.
Founder Mutation for a-sarcoglycan-LGMD2D in a Magdalen Islands Acadian Cluster
Authors: Tétreault M. , Srour M. , Allyson J. , Thiffault I. , Loisel L. , Robitaille Y. , Bouchard JP. , Brais B.
Published: February 2016

Background:

We have recruited a group of four living and reviewed the records of six deceased distantly related French-Canadians of Acadian descent affected by a childhood-onset form of recessive limb-girdle muscular dystrophy (LGMD). All cases originate from the small archipelago of the Magdalen Islands (population: 13,000) isolated in the Gulf of St-Lawrence.

Methods:

Based on the likely sharing of the same founder mutation we completed a 319K SNPs genome-wide scan to identify the disease locus and then screen candidate genes in this region.

Results:

All patients had normal initial motor milestones. They presented with limb girdle weakness at the average age of seven years (5-11). Progressive weakness led to loss of ambulation at a wide range of ages (10-39). Patients also developed macroglossia, large calves and mild to moderate contractures, hyperlordosis and decreased pulmonary function. Creatine kinase levels were elevated (1,800-10,000 U/L) in the first decades, but decreased with progression of disease. Homozygosity mapping uncovered a shared chromosomal region of 6.33Mb. The alpha sarcoglycan (SGCA) gene, mutated in LGMD2D, lay in this candidate interval. Sequencing of all SGCA exons uncovered a shared homozygous missense mutation (c.229C>T, p.R77C), the most common SGCA mutation internationally reported. Using demographic data, we estimated a high carrier rate of 1/22.

Conclusion:

The p.R77C mutation has also been observed in many populations, including in France and Spain (Basques). This corresponds to the first reported recessive founder disease for the Magdalen Islands, an archipelago settled in the XlXth century, largely by Acadian immigrants.
An International Needs Assessment of Caregivers for Frontotemporal Dementia
Authors: Chow Tiffany W. , Pio Fabricio J. , Rockwood Kenneth
Published: February 2016

Objective:

To guide development of public awareness and caregiver support resources for frontotemporal dementia (FTD) syndromes.

Methods:

We used an online survey to explore their needs. The survey was self-administered by self-identified, English-speaking caregivers for patients with FTD in several countries.

Results:

Of 79 caregiver respondents, approximately half were caring for patients with behavioural variant FTD or semantic dementia. The most common initial symptoms were Changes in Thinking and Judgment. Half of the respondents identified “failure to recognize the early stage of illness as a dementia” as the most troublesome aspect. Accordingly, over 40% of respondents had difficulty obtaining an accurate diagnosis for the patient. Caregivers prioritized family counseling and the public educational message that dementia can affect young people.

Conclusion:

The largest international survey of FTD caregivers to-date showed that support is needed for all family members adapting to the shock of early-onset dementia, and this may be most readily provided online.
Challenges and Opportunities for Water of the Rio Grande
Authors: Rister M. Edward , Sturdivant Allen W. , Lacewell Ronald D. , Michelsen Ari M.
Published: February 2016

The Rio Grande has headwaters in Colorado, flows through New Mexico, and serves as the United States-Mexico border in Texas, emptying into the Gulf of Mexico. Snow melt in Colorado and northern New Mexico constitutes the water river supply for New Mexico and the El Paso region, whereas summer monsoonal flow from the Rio Conchos in Mexico and tributaries, including the Pecos River, provides the Rio Grande flow for southern Texas. The region is mostly semiarid with frequent long-term drought periods but is also characterized by a substantial irrigated agriculture sector and a rapidly growing population. International treaties and interstate compacts provide the rules for allocation of Rio Grande waters between the United States and Mexico and among Colorado, New Mexico, and Texas. Water rights in Texas have been adjudicated, but the adjudication process was based on a wet period; hence, contemporary Rio Grande water rights are overallocated. Issues related to the waters of the Rio Grande include frequent drought, increased municipal demand caused by a rapidly increasing population, supply variability, underdeliveries from Mexico, increasing salinity, inefficient delivery systems, health issues of the population, no economic/financial incentives for farmers to conserve, and water is not typically priced for efficiency. Stakeholders are interested in identifying solutions to limited water supplies while there is increasing demand. There are several activities in place addressing Rio Grande-related water needs, including enhancing delivery distribution efficiency of raw water, conversion of rights from agriculture to urban, improving both agricultural irrigation field distribution and urban use efficiency, developments in desalination, and litigation. None of the solutions are easy or inexpensive, but there are encouraging cooperative attitudes between stakeholders.
The Utility of Self-Report Measures and the Continuous Performance Test in the Diagnosis of ADHD in Adults
Authors: Solanto Mary V. , Etefia Kenneth , Marks David J.
Published: February 2016

Background: Attention-deficit/hyperactivity disorder (ADHD) occurs in as many as 4% of adults yet it is often not recognized in clinical settings because the presenting symptoms may resemble those seen in other disorders or because symptoms may be masked by commonly comorbid conditions such as anxiety and depression.

Objective: The purpose of this study was to examine the diagnostic utility of instruments commonly used in the assessment of adults presenting with symptoms of ADHD.

Methods: We reviewed several widely used self-report and laboratory measures and empirically examined the utility of the Brown Attention-Deficit Disorder Scale for Adults (Brown ADD Scale) and the Conners Continuous Performance Test (CPT) in differentially identifying adults with ADHD and those with other Axis I disorders.

Results:Ninety-three adults who self-referred to the ADHD program for adults at a university medical center participated in the study. Of these, 44 had ADHD combined subtype (ADHD-CB), and 26 had ADHD, predominantly inattentive subtype (ADHD-IA). Thirty-three non-ADHD adults diagnosed with Axis I mood or anxiety disorders comprised an “Other Psychiatric” group. Rates of comorbid disorders, including substance abuse, in the ADHD groups were typical of those reported in the adult ADHD literature. Data on the Brown ADD Scale and on the CPT were available for subsets of 61 and 46 participants, respectively. Analyses showed that the ADHD-CB, ADHD-IA, and Other Psychiatric groups all received mean scores in the clinical range on the Brown ADD Scale, with a trend toward even higher elevations in the two ADHD groups. Among 12 CPT variables assessed for the three groups, the mean scores on only two variables for the ADHD-IA group were clinically elevated. Neither the Brown ADD Scale nor CPT scores evinced sufficient sensitivity and specificity to qualify them to assist in differential diagnosis of ADHD vis-a-vis other, predominantly internalizing, psychiatric disorders.

Conclusion: The results indicate a need for closer examination of executive and adaptive functioning in adults with ADHD compared with those with internalizing disorders in order to identify features that could assist in differential diagnosis.
Pluralistic Dialogue: A Grounded Theory of Interdisciplinary Practice
Authors: McCallin Antoinette M.
Published: February 2016

This grounded theory study explains how health professionals work in interdisciplinary teams in health services where the call for new collaborations is intensifying. Forty-four participants from four teams in two major acute-care hospitals participated in the study. In total there were eighty hours of interviewing and eighty hours of participant observation. All data were constantly compared and analysed using Glaser's emergent approach to grounded theory. Underpinning the study are the premises of symbolic interactionism that are assumed to shape the focus of this study, team interactions, and collective action within an acute care setting. The study participants' patterns of behaviour would suggest that, when interdisciplinary practice is well established, an attitude of cooperative inquiry pervades joint actions and interactions that focus on meeting service needs.
Brain Network Organization and Social Executive Performance in Frontotemporal Dementia
Authors: Sedeño Lucas , Couto Blas , García-Cordero Indira , Melloni Margherita , Baez Sandra , Morales Sepúlveda Juan Pablo , Fraiman Daniel , Huepe David , Hurtado Esteban , Matallana Diana , Kuljis Rodrigo , Torralva Teresa , Chialvo Dante , Sigman Mariano , Piguet Olivier , Manes Facundo , Ibanez Agustin
Published: February 2016

Objectives:Behavioral variant frontotemporal dementia (bvFTD) is characterized by early atrophy in the frontotemporoinsular regions. These regions overlap with networks that are engaged in social cognition-executive functions, two hallmarks deficits of bvFTD. We examine (i) whether Network Centrality (a graph theory metric that measures how important a node is in a brain network) in the frontotemporoinsular network is disrupted in bvFTD, and (ii) the level of involvement of this network in social-executive performance.Methods:Patients with probable bvFTD, healthy controls, and frontoinsular stroke patients underwent functional MRI resting-state recordings and completed social-executive behavioral measures.Results:Relative to the controls and the stroke group, the bvFTD patients presented decreased Network Centrality. In addition, this measure was associated with social cognition and executive functions. To test the specificity of these results for the Network Centrality of the frontotemporoinsular network, we assessed the main areas from six resting-state networks. No group differences or behavioral associations were found in these networks. Finally, Network Centrality and behavior distinguished bvFTD patients from the other groups with a high classification rate.Conclusions:bvFTD selectively affects Network Centrality in the frontotemporoinsular network, which is associated with high-level social and executive profile. (JINS, 2016,22, 250–262)
Salience and Default Mode Network Coupling Predicts Cognition in Aging and Parkinson’s Disease
Authors: Putcha Deepti , Ross Robert S. , Cronin-Golomb Alice , Janes Amy C. , Stern Chantal E.
Published: February 2016

Objectives:Cognitive impairment is common in Parkinson’s disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants.Methods:We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains.Results:PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson’s disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling.Conclusions:Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson’s disease. (JINS, 2016,22, 205–215)
Variation in White Matter Connectivity Predicts the Ability to Remember Faces and Discriminate Their Emotions
Authors: Unger Ashley , Alm Kylie H. , Collins Jessica A. , O’Leary Jacquelyn M. , Olson Ingrid R.
Published: February 2016

Objectives: The extended face network contains clusters of neurons that perform distinct functions on facial stimuli. Regions in the posterior ventral visual stream appear to perform basic perceptual functions on faces, while more anterior regions, such as the ventral anterior temporal lobe and amygdala, function to link mnemonic and affective information to faces. Anterior and posterior regions are interconnected by a long-range white matter tracts; however, it is not known if variation in connectivity of these pathways explains cognitive performance. Methods: Here, we used diffusion imaging and deterministic tractography in a cohort of 28 neurologically normal adults ages 18–28 to examine microstructural properties of visual fiber pathways and their relationship to certain mnemonic and affective functions involved in face processing. We investigated how inter-individual variability in two tracts, the inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF), related to performance on tests of facial emotion recognition and face memory. Results: Results revealed that microstructure of both tracts predicted variability in behavioral performance indexed by both tasks, suggesting that the ILF and IFOF play a role in facilitating our ability to discriminate emotional expressions in faces, as well as to remember unique faces. Variation in a control tract, the uncinate fasciculus, did not predict performance on these tasks. Conclusions: These results corroborate and extend the findings of previous neuropsychology studies investigating the effects of damage to the ILF and IFOF, and demonstrate that differences in face processing abilities are related to white matter microstructure, even in healthy individuals. (JINS, 2016, 22, 180–190)
Old ‘truths’, new corpora: revisiting the word order of conjunct clauses in Old English
Authors: BECH KRISTIN
Published: February 2016

In Bech (2001a, 2001b), I took issue with the oft-repeated claim that Old English conjunct main clauses are commonly verb-final, and disproved it. However, the myth persists. In the meantime, theYork–Toronto–Helsinki Parsed Corpus of Old English Prose(YCOE, Tayloret al.2003) has been created, so the time has come to revisit this topic and consider it in light of new, extensive and generally accessible data. Using the YCOE corpus, I confirm and expand on Bech's (2001a, 2001b) empirical findings, showing that (i) OE conjunct clauses are neither typically verb-final nor verb-late, but they are more frequently verb-final and verb-late than non-conjunct clauses are; and (ii) verb-final and verb-late clauses are typically conjunct clauses. These two perspectives must be kept apart: in the first, the starting point is the entire body of conjunct clauses, and in the second it is the entire body of verb-final/verb-late clauses. I propose that the failure to distinguish between the two perspectives, i.e. whether it is conjunct clauses or word order that constitutes the point of departure, is the origin of the misconception concerning conjunct clauses and word order. In order to establish whether this distinction has been fuzzy all along, or whether it must be ascribed to distorted referencing in the course of a century of research, I trace the research on this topic back to the end of the nineteenth century. I show that the alleged verb-finality of conjunct clauses may be ascribed to awhisper-down-the-laneeffect – the retelling of the story has changed the story.
The Same Difference: Protecting Same-Sex Couples under the Domestic Violence Ordinance
Authors: Kapai Puja
Published: February 2016

Hong Kong recently amended its Domestic Violence Ordinance (“DVO”). During the deliberations, the issue of whether protection under the DVO ought to be extended to same-sex couples arose for discussion and has since been the subject of extensive debate. Religious and conservative groups have argued that including these groups within the DVO risks overhauling the traditional meaning of “family” and could implicitly legitimize same-sex marriage whilst others have insisted that failing to provide equivalent civil remedies under the DVO to such groups amounts to sexual orientation discrimination and is contrary to Hong Kong's international human rights commitments. This paper reviews the various arguments that have been raised against the inclusion of same-sex couples within the DVO and argues that Hong Kong's international and constitutional commitments to the principles of equality and non-discrimination require that samesex couples be brought within the purview of this legislation.
The Validation of a Spanish Version of the Multidimensional Inventory of Religious/Spiritual Well-Being in Mexican College Students
Authors: Berger Daniela , Fink Andreas , Perez Gomez Maria Margarita , Lewis Andrew , Unterrainer Human-Friedrich
Published: February 2016

After the Multidimensional Inventory for Religious/Spiritual Well-Being (MI-RSWB) was validated as a reliable instrument for the Western European context it is primarily intended in this study to translate the measure into Spanish and adapt it for the Mexican culture. Furthermore we investigate whether spirituality/religiosity has a similar impact on indicators of personality and subjective well-being in Mexico as it does in samples drawn from Western European cultures. 190 students (99 females) from public and private universities in Guadalajara, all Mexican citizens, were involved in this study. We found strong evidential support for the six factor solution of the Original MI-RSWB in this Mexican population. By mirroring previous research the measure showed a highly satisfying internal consistency (α = .91 for the total score and .75 or higher for all six sub dimensions). Furthermore the total RSWB score was observed to be related with Eysenck’s personality dimensions Extraversion (r = .24, p < .01), and Psychoticism (r = –.28, p < .001), although not with Neuroticism. There was also a positive correlation with Sense of Coherence (r = .31, p < .001). In conclusion, the dimensionality of RSWB and its associations with personality and subjective well-being was well supported in this first application within a Mexican cultural context.
Detecting Black Carbon in the Arctic Atmosphere
Authors: Stanley Sarah
Published: February 2016

Measurements of light-absorbing carbon particles made during an Arctic research expedition could improve understanding of their effects on the Arctic climate.
Drug screening on Hutchinson Gilford progeria pluripotent stem cells reveals aminopyrimidines as new modulators of farnesylation
Authors: Blondel S , Egesipe A-L , Picardi P , Jaskowiak A-L , Notarnicola M , Ragot J , Tournois J , Le Corf A , Brinon B , Poydenot P , Georges P , Navarro C , pitrez P R , Ferreira L , Bollot G , Bauvais C , Laustriat D , Mejat A , De Sandre-Giovannoli A , Levy N , Bifulco M , Peschanski M , Nissan X
Published: February 2016

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by a dramatic appearance of premature aging. HGPS is due to a single-base substitution in exon 11 of the LMNA gene (c.1824C>T) leading to the production of a toxic form of the prelamin A protein called progerin. Because farnesylation process had been shown to control progerin toxicity, in this study we have developed a screening method permitting to identify new pharmacological inhibitors of farnesylation. For this, we have used the unique potential of pluripotent stem cells to have access to an unlimited and relevant biological resource and test 21 608 small molecules. This study identified several compounds, called monoaminopyrimidines, which target two key enzymes of the farnesylation process, farnesyl pyrophosphate synthase and farnesyl transferase, and rescue in vitro phenotypes associated with HGPS. Our results opens up new therapeutic possibilities for the treatment of HGPS by identifying a new family of protein farnesylation inhibitors, and which may also be applicable to cancers and diseases associated with mutations that involve farnesylated proteins.
The anticancer effect of chaetocin is enhanced by inhibition of autophagy
Authors: Jung H-J , Seo I , Casciello F , Jacquelin S , Lane S W , Suh S-Il , Suh M-H , Lee J S , Baek W-K
Published: February 2016

Chaetocin is a fungal metabolite that possesses a potent antiproliferative activity in solid tumors by inducing cell death. Although recent studies have extended the role of chaetocin in tumors, the underlying molecular mechanisms such as the downstream cascade that induces cell death has not clearly been elucidated. In this study, we show that chaetocin is able to induce both apoptosis and autophagy in several hepatoma cell lines including HepG2, Hep3B and Huh7 cell lines. Moreover, we found that the inhibition of caspase-3/7 activity by z-VAD-fmk treatment was able to block chaetocin-mediated cell death, whereas blocking autophagy by Bafilomycin A1 or the knockdown of autophagy protein 5 enhanced cell death mediated by chaetocin. These findings suggest that chaetocin has a potent anticancer effect against hepatoma. Inhibition of autophagy may potentiate anticancer effects of chaetocin thus providing evidence that combined treatment with chaetocin and autophagy inhibitors will be an effective strategy for treating cancer.
AIMP1 downregulation restores chondrogenic characteristics of dedifferentiated/degenerated chondrocytes by enhancing TGF-β signal
Authors: Ahn J , Kumar H , Cha B-H , Park S , Arai Y , Han I , Park S G , Lee S-H
Published: February 2016

Dedifferentiation and degeneration of chondrocytes critically influences the efficiency of cartilage repair. One of the causes is the defect of transforming growth factor (TGF)-βsignaling that promotes chondrogenic differentiation and degeneration. In the present study, we found that aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) negatively regulates TGF-βsignaling via interactions with Smad2 and Smad3 in immunoprecipitation assay and luciferase assay. In addition, we observed that the AIMP1 expression level was significantly increased in osteoarthritis (OA) patient-derived degenerated chondrocytes compared with healthy control. So, we hypothesized that downregulation of AIMP1 using small-interfering RNA (siRNA) technology in dedifferentiated (collected at passage #6) and degenerated (obtained from OA-affected areas) chondrocytes could lead to recover TGF-βsignaling in both chondrocytes. Indeed, AIMP1 downregulation restored TGF-βsignaling by promoting phosphorylation of Smad2 and Smad3, which shows redifferentiated characteristics in both dedifferentiated and degenerated chondrocytes. Additionally, implantation analyses usingin vivomouse model clearly showed that AIMP1 downregulation resulted in the increased chondrogenic potential as well as the enhanced cartilage tissue formation in both dedifferentiated and degenerated chondrocytes. Histological analyses clarified that AIMP1 downregulation increased expression levels of collagen type II (Col II) and aggrecan, but not Col I expression. Taken together, these data indicate that AIMP1 downregulation using siRNA is a novel tool to restore TGF-βsignaling and thereby increases the chondrogenic potential of dedifferentiated/degenerated chondrocytes, which could be further developed as a therapeutic siRNA to treat OA.
Altered Kv2.1 functioning promotes increased excitability in hippocampal neurons of an Alzheimer’s disease mouse model
Authors: Frazzini V , Guarnieri S , Bomba M , Navarra R , Morabito C , Mariggiò M A , Sensi S L
Published: February 2016

Altered neuronal excitability is emerging as an important feature in Alzheimer’s disease (AD). Kv2.1 potassium channels are important modulators of neuronal excitability and synaptic activity. We investigated Kv2.1 currents and its relation to the intrinsic synaptic activity of hippocampal neurons from 3xTg-AD (triple transgenic mouse model of Alzheimer's disease) mice, a widely employed preclinical AD model. Synaptic activity was also investigated by analyzing spontaneous [Ca2+]i spikes. Compared with wild-type (Non-Tg (non-transgenic mouse model)) cultures, 3xTg-AD neurons showed enhanced spike frequency and decreased intensity. Compared with Non-Tg cultures, 3xTg-AD hippocampal neurons revealed reduced Kv2.1-dependent Ik current densities as well as normalized conductances. 3xTg-AD cultures also exhibited an overall decrease in the number of functional Kv2.1 channels. Immunofluorescence assay revealed an increase in Kv2.1 channel oligomerization, a condition associated with blockade of channel function. In Non-Tg neurons, pharmacological blockade of Kv2.1 channels reproduced the altered pattern found in the 3xTg-AD cultures. Moreover, compared with untreated sister cultures, pharmacological inhibition of Kv2.1 in 3xTg-AD neurons did not produce any significant modification in Ik current densities. Reactive oxygen species (ROS) promote Kv2.1 oligomerization, thereby acting as negative modulator of the channel activity. Glutamate receptor activation produced higher ROS levels in hippocampal 3xTg-AD cultures compared with Non-Tg neurons. Antioxidant treatment with N-Acetyl-Cysteine was found to rescue Kv2.1-dependent currents and decreased spontaneous hyperexcitability in 3xTg-AD neurons. Analogous results regarding spontaneous synaptic activity were observed in neuronal cultures treated with the antioxidant 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our study indicates that AD-related mutations may promote enhanced ROS generation, oxidative-dependent oligomerization, and loss of function of Kv2.1 channels. These processes can be part on the increased neuronal excitability of these neurons. These steps may set a deleterious vicious circle that eventually helps to promote excitotoxic damage found in the AD brain.
The anti-apoptotic Bcl-2 family protein A1/Bfl-1 regulates neutrophil survival and homeostasis and is controlled via PI3K and JAK/STAT signaling
Authors: Vier J , Groth M , Sochalska M , Kirschnek S
Published: February 2016

Neutrophil granulocytes are innate effector cells of the first line of defense against pyogenic bacteria. Neutrophil lifespan is short, is prolonged by pro-inflammatory stimuli, controls functionality of the cells and can determine tissue damage. Experimental analysis of primary neutrophils is difficult because of their short lifespan and lack of possibilities of genetic manipulation. The Hoxb8 system of neutrophil differentiation from immortalized progenitor cells offers the advantage of unlimited production of neutrophils in vitro as well as easy genetic modification. We here use this system to analyze the role of the poorly characterized anti-apoptotic B-cell lymphoma protein 2 (Bcl-2) family member A1/Bfl-1 (Bcl-2-related protein A1) for survival and homeostasis of neutrophils and of neutrophil progenitors. Low constitutive mRNA and protein expression of A1 was detected, while A1 was transiently upregulated early during differentiation. Pro-inflammatory stimuli caused strong, mainly transcriptional, A1 upregulation, in contrast to posttranscriptional regulation of Mcl-1 (induced myeloid leukemia cell differentiation protein). Inhibitor studies showed that phosphoinositide-3 kinase (PI3K)/Akt and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) is required for A1 expression and survival of progenitors and mature neutrophils. ShRNA-mediated constitutive A1 knockdown (KD) impaired maintenance of progenitors. ShRNA experiments further showed that A1 was required early during neutrophil differentiation as well as in mature neutrophils upon pro-inflammatory stimulation. Our data further indicate differential regulation of the two anti-apoptotic proteins A1 and Mcl-1. Relevant findings were confirmed in primary human neutrophils. Our data indicate that A1, in addition to the well-established Mcl-1, substantially contributes to neutrophil survival and homeostasis. A1 may thus be a promising target for anti-inflammatory therapy.
Role of apoptosis-related miRNAs in resveratrol-induced breast cancer cell death
Authors: Venkatadri R , Muni T , Iyer A K V , Yakisich J S , Azad N
Published: February 2016

Breast cancer is the most frequently diagnosed cancer in women, and one of the leading causes of cancer-related deaths worldwide. Recent evidences indicate that dietary agents such as resveratrol may inhibit cancer progression through modulation of microRNAs (miRNAs). We demonstrate that resveratrol regulates apoptotic and cell cycle machinery in breast cancer cells by modulating key tumor-suppressive miRNAs including miR-125b-5p, miR-200c-3p, miR-409-3p, miR-122-5p and miR-542-3p. Resveratrol-mediated miRNA modulation regulates key anti-apoptotic and cell cycle proteins including Bcl-2, X-linked inhibitor of apoptosis protein and CDKs, which are critical for its activity. Modulating miRNAs with mimics or inhibitors further validated a key role for miR-542-3p in MCF-7 and miR-122-5p in MDA-MB-231 breast cancer cell death in response to resveratrol. In conclusion, this study reveals novel miRNAs modulated by resveratrol that have a key role in breast cancer cell death.
A naturally occurring transcript variant of MARCO reveals the SRCR domain is critical for function
Authors: Novakowski Kyle E , Huynh Angela , Han SeongJun , Dorrington Michael G , Yin Charles , Tu Zhongyuan , Pelka Peter , Whyte Peter , Guarné Alba , Sakamoto Kaori , Bowdish Dawn M E
Published: February 2016

Macrophage receptor with collagenous structure (MARCO) is a class A scavenger receptor (cA‐SR) that recognizes and phagocytoses a wide variety of pathogens. Most cA‐SRs that contain a C‐terminal scavenger receptor cysteine‐rich (SRCR) domain use the proximal collagenous domain to bind ligands. In contrast, the role of the SRCR domain of MARCO in phagocytosis, adhesion and pro‐inflammatory signaling is less clear. The discovery of a naturally occurring transcript variant lacking the SRCR domain, MARCOII, provided the opportunity to study the role of the SRCR domain of MARCO. We tested whether the SRCR domain is required for ligand binding, promoting downstream signaling and enhancing cellular adhesion. Unlike cells expressing full‐length MARCO, ligand binding was abolished in MARCOII‐expressing cells. Furthermore, co‐expression of MARCO and MARCOII impaired phagocytic function, indicating that MARCOII acts as a dominant‐negative variant. Unlike MARCO, expression of MARCOII did not enhance Toll‐like receptor 2 (TLR2)‐mediated pro‐inflammatory signaling in response to bacterial stimulation. MARCO‐expressing cells were more adherent and exhibited a dendritic‐like phenotype, whereas MARCOII‐expressing cells were less adherent and did not exhibit changes in morphology. These data suggest the SRCR domain of MARCO is the key domain in modulating ligand binding, enhancing downstream pro‐inflammatory signaling and MARCO‐mediated cellular adhesion.
β‐Adrenergic receptor agonist, compound 49b, inhibits TLR4 signaling pathway in diabetic retina
Authors: Berger Elizabeth A , Carion Thomas W , Jiang Youde , Liu Li , Chahine Adam , Walker Robert Jason , Steinle Jena J
Published: February 2016

Diabetic retinopathy has recently become associated with complications similar to chronic inflammatory diseases. Although it is clear that tumor necrosis factor‐α is increased in diabetes, the role of innate immunity is only recently being investigated. As such, we hypothesized that diabetes would increase Toll‐like receptor 4 (TLR4) signaling, which could be inhibited by a β‐adrenergic receptor agonist (Compound 49b) previously shown to have anti‐inflammatory actions. In order to investigate β‐adrenergic receptor signaling and TLR4 in the diabetic retina, streptozotocin‐injected diabetic mice, as well as human primary retinal endothelial cells (RECs) and rat retinal Müller cells (rMC‐1) exposed to high glucose (25 mm), were treated with a novel β‐adrenergic receptor agonist, Compound 49b (50 nm), or phosphate‐buffered saline (control). TLR4 and its downstream signaling partners (MyD88, IL‐1 receptor‐associated kinase 1, TNF receptor‐associated factor 6 and total and phosphorylated nuclear factor‐κB) were examined. In addition, we assessed high‐mobility group box 1 (HMGB1) protein levels. Our data showed that diabetes or high‐glucose culture conditions significantly increased TLR4 and downstream signaling partners. Compound 49b was able to significantly reduce TLR4 and related molecules in the diabetic animal and retinal cells. HMGB1 was significantly increased in RECs and Müller cells grown in high‐glucose culture conditions, which was subsequently reduced with Compound 49b treatment. Our findings suggest that high glucose may increase HMGB1 levels that lead to increased TLR4 signaling. Compound 49b significantly inhibited this pathway, providing a potential mechanism for its protective actions.
Accurate prediction of cellular co-translational folding indicates proteins can switch from post- to co-translational folding
Authors: Nissley Daniel A. , Sharma Ajeet K. , Ahmed Nabeel , Friedrich Ulrike A. , Kramer Günter , Bukau Bernd , O’Brien Edward P.
Published: February 2016

The rates at which domains fold and codons are translated are important factors in determining whether a nascent protein will co-translationally fold and function or misfold and malfunction. Here we develop a chemical kinetic model that calculates a protein domain’s co-translational folding curve during synthesis using only the domain’s bulk folding and unfolding rates and codon translation rates. We show that this model accurately predicts the course of co-translational folding measured in vivo for four different protein molecules. We then make predictions for a number of different proteins in yeast and find that synonymous codon substitutions, which change translation-elongation rates, can switch some protein domains from folding post-translationally to folding co-translationally—a result consistent with previous experimental studies. Our approach explains essential features of co-translational folding curves and predicts how varying the translation rate at different codon positions along a transcript’s coding sequence affects this self-assembly process.