bluuebunny/crossref_metadata_2025 huggingface dataset:
NAD+ consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival
Authors: Murata Michael M. , Kong Xiangduo , Moncada Emmanuel , Chen Yumay , Imamura Hiromi , Wang Ping , Berns Michael W. , Yokomori Kyoko , Digman Michelle A.
Published: August 2019

DNA damage signaling is critical for the maintenance of genome integrity and cell fate decision. Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor rapidly activated in a damage dose- and complexity-dependent manner playing a critical role in the initial chromatin organization and DNA repair pathway choice at damage sites. However, our understanding of a cell-wide consequence of its activation in damaged cells is still limited. Using the phasor approach to fluorescence lifetime imaging microscopy and fluorescence-based biosensors in combination with laser microirradiation, we found a rapid cell-wide increase of the bound NADH fraction in response to nuclear DNA damage, which is triggered by PARP-dependent NAD+ depletion. This change is linked to the metabolic balance shift to oxidative phosphorylation (oxphos) over glycolysis. Inhibition of oxphos, but not glycolysis, resulted in parthanatos due to rapid PARP-dependent ATP deprivation, indicating that oxphos becomes critical for damaged cell survival. The results reveal the novel prosurvival response to PARP activation through a change in cellular metabolism and demonstrate how unique applications of advanced fluorescence imaging and laser microirradiation-induced DNA damage can be a powerful tool to interrogate damage-induced metabolic changes at high spatiotemporal resolution in a live cell.
Coordination of protrusion dynamics within and between collectively migrating border cells by myosin II
Authors: Mishra Abhinava K. , Mondo James A. , Campanale Joseph P. , Montell Denise J.
Published: August 2019

Collective cell migration is emerging as a major driver of embryonic development, organogenesis, tissue homeostasis, and tumor dissemination. In contrast to individually migrating cells, collectively migrating cells maintain cell–cell adhesions and coordinate direction-sensing as they move. While nonmuscle myosin II has been studied extensively in the context of cells migrating individually in vitro, its roles in cells migrating collectively in three-dimensional, native environments are not fully understood. Here we use genetics, Airyscan microscopy, live imaging, optogenetics, and Förster resonance energy transfer to probe the localization, dynamics, and functions of myosin II in migrating border cells of the Drosophila ovary. We find that myosin accumulates transiently at the base of protrusions, where it functions to retract them. E-cadherin and myosin colocalize at border cell-border cell contacts and cooperate to transmit directional information. A phosphomimetic form of myosin is sufficient to convert border cells to a round morphology and blebbing migration mode. Together these studies demonstrate that distinct and dynamic pools of myosin II regulate protrusion dynamics within and between collectively migrating cells and suggest a new model for the role of protrusions in collective direction sensing in vivo.
Social factors, not anthropogenic noise or artificial light, influence onset of dawn singing in a common songbird
Authors: Stuart Carley J , Grabarczyk Erin E , Vonhof Maarten J , Gill Sharon A
Published: August 2019

With worldwide increases in artificial light and anthropogenic noise, understanding how these pollutants influence animals allows us to better mitigate potential negative effects. Both light and noise affect the timing of daily activities, including the onset of dawn song in birds, yet the influence of these pollutants compared with social factors that also influence song onset remains unknown. We investigated the onset of dawn song, testing hypotheses aimed at understanding the influences of light and noise pollution as well as male competition, pairing status, and breeding stage on timing of dawn singing by male House Wrens (Troglodytes aedon). Overall, models with social factors fit song onset data better than models with abiotic factors of noise and sky glow, and the highest ranking model included nesting stage, number of male neighbors, and temperature. Males began singing earlier when they were building nests and when mates were fertile than during later nesting stages. Males also sang earlier as the number of male neighbors increased. The timing of dawn song by male House Wrens appeared unaffected by day-to-day variation in light and noise pollution, with social factors having larger effects on the onset of daily behavior in this species.
RICOPILI: Rapid Imputation for COnsortias PIpeLIne
Authors: Lam Max , Awasthi Swapnil , Watson Hunna J , Goldstein Jackie , Panagiotaropoulou Georgia , Trubetskoy Vassily , Karlsson Robert , Frei Oleksander , Fan Chun-Chieh , De Witte Ward , Mota Nina R , Mullins Niamh , Brügger Kim , Lee S Hong , Wray Naomi R , Skarabis Nora , Huang Hailiang , Neale Benjamin , Daly Mark J , Mattheisen Manuel , Walters Raymond , Ripke Stephan
Published: August 2019

Genome-wide association study (GWAS) analyses, at sufficient sample sizes and power, have successfully revealed biological insights for several complex traits. RICOPILI, an open-sourced Perl-based pipeline was developed to address the challenges of rapidly processing large-scale multi-cohort GWAS studies including quality control (QC), imputation and downstream analyses. The pipeline is computationally efficient with portability to a wide range of high-performance computing environments. RICOPILI was created as the Psychiatric Genomics Consortium pipeline for GWAS and adopted by other users. The pipeline features (i) technical and genomic QC in case-control and trio cohorts, (ii) genome-wide phasing and imputation, (iv) association analysis, (v) meta-analysis, (vi) polygenic risk scoring and (vii) replication analysis. Notably, a major differentiator from other GWAS pipelines, RICOPILI leverages on automated parallelization and cluster job management approaches for rapid production of imputed genome-wide data. A comprehensive meta-analysis of simulated GWAS data has been incorporated demonstrating each step of the pipeline. This includes all the associated visualization plots, to allow ease of data interpretation and manuscript preparation. Simulated GWAS datasets are also packaged with the pipeline for user training tutorials and developer work.

Availability and implementation

RICOPILI has a flexible architecture to allow for ongoing development and incorporation of newer available algorithms and is adaptable to various HPC environments (QSUB, BSUB, SLURM and others). Specific links for genomic resources are either directly provided in this paper or via tutorials and external links. The central location hosting scripts and tutorials is found at this URL: https://sites.google.com/a/broadinstitute.org/RICOPILI/home

Supplementary information

Supplementary data are available at Bioinformatics online.
Mitochondrial DNA copy number in peripheral blood leukocytes is associated with biochemical recurrence in prostate cancer patients in African Americans
Authors: Xu Junfeng , Chang Wen-Shin , Tsai Chia-Wen , Bau Da-Tian , Davis John W , Thompson Timothy C , Logothetis Christopher J , Gu Jian
Published: August 2019

Mitochondria play multiple important cellular functions. The purpose of this study was to evaluate whether leukocyte mitochondrial DNA copy number (mtDNAcn) is associated with aggressive prostate cancer (PCa) in African American (AA) men. We measured the mtDNAcn in peripheral blood leukocytes from 317 localized AA PCa patients and evaluated its associations with aggressive disease features at diagnosis and biochemical recurrence (BCR) after treatments. There was no significant difference in mtDNAcn among the clinical features at diagnosis, including age, prostate-specific antigen level, Gleason score and clinical stage under analysis of variance test. However, mtDNAcn was significantly associated with BCR in multivariate Cox analysis. Dichotomized into low and high mtDNAcn groups by the median value of mtDNAcn, patients with low mtDNAcn exhibited a significantly lower risk of BCR (hazard ratio = 0.32, 95% confidence interval: 0.13–0.79) compared to those with high mtDNAcn. There was a significant dose–response in tertile and quartile analyses (P for trend = 0.012 and 0.002, respectively). In Kaplan–Meier survival analyses, patients with higher mtDNAcn exhibited significantly shorter BCR-free survival time than those with lower mtDNAcn in dichotomous, tertile and quartile analyses, with long-rank P values of 0.017, 0.024 and 0.019, respectively. Our results showed for the first time that high leukocyte mtDNAcn was associated with worse prognosis in AA PCa patients.
Inhibitory Theta Burst Stimulation Highlights the Role of Left aIPS and Right TPJ during Complementary and Imitative Human–Avatar Interactions in Cooperative and Competitive Scenarios
Authors: Era Vanessa , Aglioti Salvatore Maria , Candidi Matteo
Published: August 2019

Competitive and cooperative interactions are based on anticipation or synchronization with the partner’s actions. Both forms of interaction may either require performing imitative or complementary movements with respect to those performed by our partner. We explored how parietal regions involved in the control of imitative behavior (temporo-parietal junction, TPJ), goal coding and visuo-motor integration (anterior intraparietal sulcus, aIPS) contribute to the execution of imitative and complementary movements during cooperative and competitive interactions. To this aim, we delivered off-line non-invasive inhibitory brain stimulation to healthy individuals’ left aIPS and right TPJ before they were asked to reach and grasp an object together with a virtual partner by either performing imitative or complementary interactions. In different blocks, participants were asked to compete or cooperate with the virtual partner that varied its behavior according to cooperative or competitive contexts. Left aIPS and right TPJ inhibition impaired individuals’ performance (i.e., synchrony in cooperative task and anticipation in competition) during complementary and imitative interactions, respectively, in both cooperative and competitive contexts, indicating that aIPS and TPJ inhibition affects own-other action integration and action imitation (that are different in complementary vs imitative interactions) more than action synchronization or anticipation (that are different in cooperative vs competitive contexts).
Declining Trends of Pneumococcal Meningitis in Gambian Children After the Introduction of Pneumococcal Conjugate Vaccines
Authors: Sanneh Bakary , Okoi Catherine , Grey-Johnson Mary , Bah-Camara Haddy , Kunta Fofana Baba , Baldeh Ignatius , Papa Sey Alhagie , Labbo Bah Mahamadou , Cham Mamadi , Samateh Amadou , Usuf Effua , Ndow Peter Sylvanus , Senghore Madikay , Worwui Archibald , Mwenda Jason M , Kwambana-Adams Brenda , Antonio Martin
Published: August 2019

Background

Acute bacterial meningitis remains a major cause of childhood mortality in sub-Saharan Africa. We document findings from hospital-based sentinel surveillance of bacterial meningitis among children <5 years of age in The Gambia, from 2010 to 2016.

Methods

Cerebrospinal fluid (CSF) was collected from children admitted to the Edward Francis Small Teaching Hospital with suspected meningitis. Identification of Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae was performed by microbiological culture and/or polymerase chain reaction where possible. Whole genome sequencing was performed on pneumococcal isolates.

Results

A total of 438 children were admitted with suspected meningitis during the surveillance period. The median age of the patients was 13 (interquartile range, 3–30) months. Bacterial meningitis was confirmed in 21.4% (69/323) of all CSF samples analyzed. Pneumococcus, meningococcus, and H. influenzae accounted for 52.2%, 31.9%, and 16.0% of confirmed cases, respectively. There was a significant reduction of pneumococcal conjugate vaccine (PCV) serotypes, from 44.4% in 2011 to 0.0% in 2014, 5 years after PCV implementation. The majority of serotyped meningococcus and H. influenzae belonged to meningococcus serogroup W (45.5%) and H. influenzae type b (54.5%), respectively. Meningitis pathogens were more frequently isolated during the dry dusty season of the year. Reduced susceptibility to tetracycline, trimethoprim-sulfamethoxazole, and chloramphenicol was observed. No resistance to penicillin was found.

Conclusions

The proportion of meningitis cases due to pneumococcus declined in the post-PCV era. However, the persistence of vaccine-preventable meningitis in children aged <5 years is a major concern and demonstrates the need for sustained high-quality surveillance.
Therapeutic inhibition of microRNA-34a ameliorates aortic valve calcification via modulation of Notch1-Runx2 signalling
Authors: Toshima Taku , Watanabe Tetsu , Narumi Taro , Otaki Yoichiro , Shishido Tetsuro , Aono Tomonori , Goto Jun , Watanabe Ken , Sugai Takayuki , Takahashi Tetsuya , Yokoyama Miyuki , Kinoshita Daisuke , Tamura Harutoshi , Kato Shigehiko , Nishiyama Satoshi , Arimoto Takanori , Takahashi Hiroki , Miyamoto Takuya , Sadahiro Mitsuaki , Watanabe Masafumi
Published: August 2019

Aims

Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease and is increased with elderly population. However, effective drug therapy has not been established yet. This study aimed to investigate the role of microRNAs (miRs) in the development of CAVS.

Methods and results

We measured the expression of 10 miRs, which were reportedly involved in calcification by using human aortic valve tissue from patients who underwent aortic valve replacement with CAVS or aortic regurgitation (AR) and porcine aortic valve interstitial cells (AVICs) after treatment with osteogenic induction medium. We investigated whether a specific miR-inhibitor can suppress aortic valve calcification in wire injury CAVS mice model. Expression of miR-23a, miR-34a, miR-34c, miR-133a, miR-146a, and miR-155 was increased, and expression of miR-27a and miR-204 was decreased in valve tissues from CAVS compared with those from AR. Expression of Notch1 was decreased, and expression of Runt-related transcription factor 2 (Runx2) was increased in patients with CAVS compared with those with AR. We selected miR-34a among increased miRs in porcine AVICs after osteogenic treatment, which was consistent with results from patients with CAVS. MiR-34a increased calcium deposition in AVICs compared with miR-control. Notch1 expression was decreased, and Runx2 expression was increased in miR-34a transfected AVICs compared with that in miR-control. Conversely, inhibition of miR-34a significantly attenuated these calcification signals in AVICs compared with miR-control. RNA pull-down assay revealed that miR-34a directly targeted Notch1 expression by binding to Notch1 mRNA 3′ untranslated region. In wire injury CAVS mice, locked nucleic acid miR-34a inhibitor suppressed aortic velocity, calcium deposition of aortic valves, and cardiac hypertrophy, which were involved in decreased Runx2 and increased Notch1 expressions.

Conclusion

miR-34a plays an important role in the development of CAVS via Notch1–Runx2 signalling pathway. Inhibition of miR-34a may be the therapeutic target for CAVS.
Lazarus in asystole: a case report of autoresuscitation after prolonged cardiac arrest
Authors: Sprenkeler David J , van Hout Gerardus P J , Chamuleau Steven A J
Published: August 2019

Background

Third-degree atrioventricular (AV) block can result in sudden cardiac death if no reliable escape rhythm is present. Here, we report a case of an 86-year-old female patient who developed a third-degree AV block leading to cardiac arrest. Surprisingly, sinus rhythm returned after 4 min of asystole, and she showed complete neurological recovery.

Case summary

Emergency services were contacted by the husband of an 86-year-old woman after she was found unconscious. Ambulance personnel diagnosed a third-degree AV block without an escape rhythm and transcutaneous pacing was started. At arrival on the emergency ward, pacing was inadequate, resulting in absence of circulation for ∼10 min. After consultation with the family, the patient turned out to have signed a ‘do not resuscitate’ order. Given the impression that the considerable delay deemed favourable neurological recovery unlikely, it was decided together with the family to stop the resuscitation. Subsequently, she had an intermittent junctional escape rhythm but eventually developed a documented asystole of more than 4 min. Against all expectations, she regained sinus rhythm and fully recovered. Eventually, a pacemaker was implanted and she was discharged home without neurological sequalae of the cardiac arrest.

Discussion

Autoresuscitation, also known as the Lazarus syndrome, is the spontaneous return of circulation after cardiac arrest and is incidentally seen after failed cardiopulmonary resuscitation (CPR). Autoresuscitation in the absence of CPR is highly unusual, but could, in this case, be due to the total AV block as the cause of the cardiac arrest.
Intestinal Clostridium species lower host susceptibility to enterohemorrhagic Escherichia coli O157:H7 infection
Authors: Koyanagi Yukako , Suzuki Rie , Ihara Kohei , Miyagi Hikaru , Isogai Hiroshi , Yoneyama Hiroshi , Isogai Emiko
Published: August 2019

Susceptibility to enterohemorrhagic Escherichia coli (EHEC) infection varies among humans. The intestinal microbiota seems to play an essential role in host defense against EHEC; thus, we hypothesized that indigenous bacteria, such as Clostridium ramosum and Clostridium perfringens, could influence the susceptibility to EHEC infection. To evaluate the effect of indigenous bacteria on EHEC infection, germ-free mice were precolonized with each indigenous bacterium, and then infected with EHEC O157:H7. Precolonization with C. ramosum or C. perfringens completely prevented death from EHEC infection througout a test period. Precolonization with C. ramosum also reduced the level of secreted Shiga toxin (Stx) 2 and prevented histopathological changes in the kidneys in a similar way to precolonization with Bifidobacterium longum, which is used as a model for preventing EHEC infection. In contrast, the mice precolonized with C. perfringens showed mild renal injuries. When evaluated using an in vitro co-culturing system, again C. ramosum inhibited the growth and Stx production of EHEC more potently than C. perfringens. These results indicate that C. ramosum and C. perfringens suppressed EHEC infection; however, the extent of their preventive effects differed. Therefore, the susceptibility to EHEC infection and its severity can depend on the functional bacteria present in the intestinal microbiota of individuals.
Major Depressive Disorder (MDD) and Schizophrenia– Addressing Unmet Needs With Partial Agonists at the D2 Receptor: A Review
Authors: Mallet Jasmina , Gorwood Philip , Le Strat Yann , Dubertret Caroline
Published: August 2019

Second-generation antipsychotics are common candidates for the adjunctive treatment of major depressive disorder and for the treatment of schizophrenia. However, unmet needs remain in the treatment of both disorders. Considering schizophrenia, antipsychotics are the most common treatment and have demonstrated good efficacy. Still, side effects of these treatments are commonly reported and may impact adherence to the medication and functioning in patients with schizophrenia. Regarding major depressive disorder, despite the availability of several classes of antidepressants, many patients do not achieve remission. Adjunctive treatment with antipsychotics may improve clinical and functional outcomes. Compared with dopamine D2 receptor antagonism that is exhibited by most antipsychotics, partial agonism may result in improved outcomes in major depressive disorder and in schizophrenia. Aripiprazole, cariprazine, and brexpiprazole have partial agonism at the dopamine D2 receptor and could potentially overcome limitations associated with D2 antagonism. The objectives of this review were (1) to discuss the goal of treatment with second-generation antipsychotics in major depressive disorder and schizophrenia, and the clinical factors that should be considered, and (2) to examine the short- and long-term existing data on the efficacy and safety of D2 receptor partial agonists (aripiprazole, cariprazine, and brexpiprazole) in the adjunctive treatment of major depressive disorder and in the treatment of schizophrenia.
Emergence of NDM-producing Klebsiella pneumoniae and Escherichia coli in Spain: phylogeny, resistome, virulence and plasmids encoding blaNDM-like genes as determined by WGS
Authors: Pérez-Vázquez María , Sola Campoy Pedro J , Ortega Adriana , Bautista Verónica , Monzón Sara , Ruiz-Carrascoso Guillermo , Mingorance Jesus , González-Barberá Eva M , Gimeno Concepción , Aracil Belén , Sáez David , Lara Noelia , Fernández Sara , González-López Juan José , Campos José , Kingsley Robert A , Dougan Gordon , Oteo-Iglesias Jesús ,   Spanish NDM Study Group, Rodrigo Cristina Herrera , Aznar Esteban , García-Picazo Luisa , Martínez Beatriz Orden , Mansilla Emilia Cercenado , Álvarez-García Patricia , Carretero Julia María Pita , Rodríguez-Conde Irene , Cao Sonia María Rey , Gimeno Adelina , Moreno Mar Olga Pérez , Rodríguez Ma Luz Cordón , Cavero Teresa Alarcón , Gil Yolanda , Esteras Ma Antonia Remacha , Andrés José Luis Barrios , Trujillo Gloria , Almaraz José Luis Hernández , José Luis del Pozo José Leiva León y , Salas Carmen Martín , Adán Fernando Buñuel , Bertomeu Frederic Gómez , Cascales Paloma , Dorado José Cobos , Suarez Concepción Balado
Published: August 2019

Objectives

NDM carbapenemases have spread worldwide. However, little information exists about the impact of NDM-producing Enterobacteriaceae in Spain. By WGS, we sought to elucidate the population structure of NDM-like-producing Klebsiella pneumoniae and Escherichia coli in Spain and to determine the plasmids harbouring blaNDM-like genes.

Methods

High-resolution SNP typing, core-genome MLST and plasmid reconstruction (PlasmidID) were performed on 59 NDM-like-producing K. pneumoniae and 8 NDM-like-producing E. coli isolated over an 8 year period in Spain.

Results

Five major epidemic clones of NDM-producing K. pneumoniae caused five important nationwide outbreaks: ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1; in contrast, the spread of NDM-producing E. coli was polyclonal. Three blaNDM types were identified: blaNDM-1, 61.2%; blaNDM-7, 32.8%; and blaNDM-5, 6%. Five K. pneumoniae isolates co-produced other carbapenemases (three blaOXA-48 and two blaVIM-1). The average number of acquired resistance genes was higher in K. pneumoniae than in E. coli. The plasmids encoding blaNDM-like genes belonged to IncFII, IncFIB, IncX3, IncR, IncN and IncC types, of which IncF, IncR and IncC were associated with MDR. The genetic surroundings of blaNDM-like genes showed a highly variable region upstream of ISAba125.

Conclusions

In recent years NDM-producing K. pneumoniae and E. coli have emerged in Spain; the spread of a few high-risk K. pneumoniae clones such as ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1 have caused several interregional outbreaks. In contrast, the spread of NDM-producing E. coli has been polyclonal. Plasmid types IncFII, IncFIB, IncX3, IncR, IncN and IncC carried blaNDM, and the same IncX3 plasmid was detected in K. pneumoniae and E. coli.
miR-211-5p contributes to chondrocyte differentiation by suppressing Fibulin-4 expression to play a role in osteoarthritis
Authors: Liu Hao , Luo Jun
Published: August 2019

MicroRNAs (miRNAs) serve as key regulators in human disorders. Previous research reported that miR-211-5p is down-regulated in osteoarthritis (OA) and that Fibulin-4 inhibits chondrocyte differentiation. However, the role of miR-211-5p in the development of OA has not been clarified, and its downstream target has not been studied. This study aimed to explore the effect of miR-211-5p on chondrocyte differentiation and its influence on OA pathogenesis, as well as the interaction between miR-211-5p and Fibulin-4. In this study, we found that miR-211-5p is significantly down-regulated in articular cartilage tissues in an OA rat model, whereas it is clearly up-regulated during chondrocyte differentiation of ATDC5 cells. Silencing miR-211-5p in ATDC5 cells had an adverse effect on chondrocyte differentiation. Fibulin-4 was identified as a target of miR-211-5p, and miR-211-5p participated in chondrocyte differentiation by negatively regulating Fibulin-4 expression. In the OA rat model, miR-211-5p overexpression facilitated chondrocyte differentiation, along with the reduced pro-inflammatory cytokines level and the level of proteinases responsible for cartilage matrix degradation. In summary, miR-211-5p promotes chondrocyte differentiation by negatively regulating Fibulin-4 expression, and represses the expression of pro-inflammatory cytokines and proteinases responsible for cartilage matrix degradation in OA. miR-211-5p may serve as a promising target for OA treatment.
Physiological and behavioral responses to anthropogenic stressors in a human-tolerant mammal
Authors: Hammond Talisin T , Vo Minnie , Burton Clara T , Surber Lisa L , Lacey Eileen A , Smith Jennifer E
Published: August 2019

As humans continue to alter natural habitats, many wild animals are facing novel suites of environmental stimuli. These changes, including increased human–wildlife interactions, may exert sublethal impacts on wildlife such as alterations in stress physiology and behavior. California ground squirrels (Otospermophilus beecheyi) occur in human-modified as well as more pristine environments, where they face a variety of anthropogenic and naturally occurring threats. This makes this species a valuable model for examining the effects of diverse challenges on the physiology and behavior of free-living mammals. To explore potential sublethal effects of habitat modification on O. beecheyi, we compared body masses, behaviors, and fecal glucocorticoid metabolite (FGM) levels for free-living squirrels in human-disturbed versus undisturbed habitats. Prior to these analyses, we validated the use of FGMs in this species by exposing captive O. beecheyi to pharmacological and handling challenges; both challenges produced significant increases in FGMs in the study animals. While FGM responses were repeatable within captive individuals, responses by free-living animals were more variable, perhaps reflecting a greater range of life-history traits and environmental conditions within natural populations of squirrels. Animals from our human-disturbed study site had significantly higher FGMs, significantly lower body masses, and were significantly less behaviorally reactive to humans than those from our more pristine study site. Thus, despite frequent exposure of California ground squirrels to human impacts, anthropogenic stressors appear to influence stress physiology and other phenotypic traits in this species. These findings suggest that even human-tolerant mammalian species may experience important sublethal consequences due to human modifications of natural habitats.
Safer food through plant science: reducing toxic element accumulation in crops
Authors: Clemens Stephan
Published: August 2019

The accumulation of toxic elements in crops is associated with human health risks. Rapid progress towards a mechanistic understanding now enables the engineering of much safer crop varieties.
GABA operates upstream of H+-ATPase and improves salinity tolerance in Arabidopsis by enabling cytosolic K+ retention and Na+ exclusion
Authors: Su Nana , Wu Qi , Chen Jiahui , Shabala Lana , Mithöfer Axel , Wang Haiyang , Qu Mei , Yu Min , Cui Jin , Shabala Sergey
Published: August 2019

GABA has beneficial effects on salinity stress tolerance in Arabidopsis linked to increased activity of H+-ATPase, reduced ROS-induced K+ efflux from root epidermis, and increased SOS1 and NHX1 transcript levels in plant roots.
Nitrate transporter 1.1 alleviates lead toxicity in Arabidopsis by preventing rhizosphere acidification
Authors: Zhu Jun , Fang Xian Zhi , Dai Yu Jie , Zhu Ya Xin , Chen Hong Shan , Lin Xian Yong , Jin Chong Wei
Published: August 2019

Exposure to Pb2+ increases NRT1.1-mediated uptake of nitrate in Arabidopsis and is associated with decreased uptake of Pb into the plant, which is a consequence of decreased acidification in the rhizosphere.
Pathophysiology of Signs and Symptoms of Coma
Authors: Posner Jerome B. , Saper Clifford B. , Schiff Nicholas D. , Claassen Jan
Published: August 2019

Chapter 1 provides some important background information on the pathophysiology of impaired consciousness, as well as on the signs and symptoms that accompany it. It starts with definitions of key terms: consciousness, acutely altered states of consciousness, and subacute or chronic alterations of consciousness, as well as the definitions for stupor, coma, and other states of altered consciousness. It looks at how to approach the diagnosis of the comatose patient, and it then explains the physiology and pathophysiology of consciousness and coma. Finally, it describes three types of brain damage that may lead to altered consciousness or coma: bilateral hemispheric damage, diencephalic injury, and upper brainstem injury.
Prognosis in Coma and Related Disorders of Consciousness and Mechanisms Underlying Outcomes
Authors: Posner Jerome B. , Saper Clifford B. , Schiff Nicholas D. , Claassen Jan
Published: August 2019

This chapter looks at the difficulty in predicting the outcome for patients with severe brain damage. Brain death, in principle, is conceptually a single biologic state with an unequivocal future, while severe brain injuries span a wide range of outcomes depending on a number of variables that include not only the degree of neurologic injury, but also the presence and severity of medical complications. The chapter looks in detail at the process of recovery after coma. It examines the various factors that influence recovery, such as duration of coma, presence of secondary injuries, age, motor findings, biochemical markers, electrophysiological markers, and multivariate modeling. It looks at a number of underlying causes of coma and how they relate to prognosis.
Disorders of Consciousness in Clinical Practice
Authors: Fins Joseph J.
Published: August 2019

“Disorders of Consciousness in Clinical Practice” considers the ethical, legal, and policy considerations of working with patients and families with severe brain injury. Topics include professional obligations to patients with disorders of consciousness and the ethical implications of coma, brain death and the vegetative and minimally conscious state as well as their diagnostic classification based on behavioral and neuroimaging assessment. The normative challenge of covert consciousness is considered. Clinical, ethical and communication strategies for working with patients with impaired decision-making capacity and their families and surrogates are presented along a typical trajectory of care from initial presentation, intensive care, and discharge to rehabilitation and/or long-term care. End-of-life care, neuropalliation, and bereavement are also discussed as are ancillary care obligations to this marginalized and vulnerable population. Broader policy needs such as access to care is discussed in the context of civil and disability rights.
Deprescribing in Psychiatry
Authors: Gupta Swapnil , Cahill John , Miller Rebecca
Published: August 2019

With the growth of polypharmacy across medicine, the concept of deprescribing—reducing or eliminating the use of medication—is gaining traction among prescribers in a range of specialties. Applying this concept to psychiatry is more complex than in other fields of medicine and requires expanding the intervention to include consideration of psychological, social, environmental, and cultural factors. Taking a recovery-oriented and strengths-based approach, this book outlines the need for deprescribing in psychiatry and expands on the intervention to look at barriers and strategies for addressing them, as well as specific considerations for classes of psychotropic medications. The book is explicitly not against the use of medications but instead promotes a rational approach to considering the reduction of medications when indicated and when agreed upon by both prescriber and patient by promoting the use of shared decision-making and working to minimize risk while maximizing quality of life. The book includes learning objectives, self-assessment quizzes, and case examples to support the reader and provide concrete illustrations of implementation. It is geared toward all prescribers of psychiatric medications and is useful as well for patients, family members, and other mental health practitioners interested in learning more about approaches to making the best, most judicious use of psychiatric medications in mental health.
Decision-Making in Deprescribing
Authors: Gupta Swapnil , Miller Rebecca , Cahill John D.
Published: August 2019

This chapter discusses a framework for psycho-pharmacological decision-making and its applications specifically in the context of deprescribing. It introduces concepts and considerations involved in implementing shared decision-making, including how to create a constructive environment for conversations, stages of shared decision-making, and factors to consider that may impact both the provider and the patient. These decisions are especially difficult when doctors and patients disagree, when values or preferences conflict with standard guidelines, or simply when no guidelines are available. Identifying possible bias against making changes in medication regimens is highlighted, as well as the importance of honoring cultural preferences in the decision-making process.
Nonpharmacological Aspects of Deprescribing
Authors: Gupta Swapnil , Miller Rebecca , Cahill John D.
Published: August 2019

This chapter discusses the possible psychological and social impacts of deprescribing that may emerge when initiating a course of deprescribing. These may include anticipated reactions from family members, treaters, and systems, each of which deserves addressing in the context of the intervention in order to best facilitate deprescribing. These reactions may include real and imagined consequences for a patient, family and friends, treater, and systems (such as altered access to resources/entitlements). By understanding and considering these nonpharmacological aspects of the intervention, prescribers may better anticipate otherwise unforeseen pitfalls in the process. Strategies for eliciting and addressing these concerns are discussed.
Wellness Approaches I
Authors: Gupta Swapnil , Miller Rebecca , Cahill John D.
Published: August 2019

Some patients and their support systems may interpret an attempt at deprescribing as a withdrawal of treatment or care. The prescriber must work to counter this perception by acknowledging the problem and by bolstering existing strategies or introducing and developing, along with the patient, new strategies for maintaining wellness.

Deprescribing prompts an excellent opportunity for an individual to expand supports and wellness strategies. This chapter discusses those strategies initiated by the person in order to maintain wellness and manage any symptoms that emerge during the process. These include using a preplanning tool such as a Wellness Recovery Action Plan (WRAP) or others to develop and articulate needed supports and preferences in case of crisis. Exercise, family support, and finding meaning and purpose are also discussed in this chapter.
Deprescribing Mood Stabilizers
Authors: Gupta Swapnil , Miller Rebecca , Cahill John D.
Published: August 2019

This chapter reviews the literature on lithium withdrawal and provides strategies on how to reduce the risk of relapse through such measures as slow tapers. Combinations of mood stabilizers such as lithium, divalproex, carbamazepine, and lamotrigine are used frequently and recommended even with the approval of several second-generation antipsychotic medications as mood stabilizers. As patients grow older, the potential nephrotoxicity and hepatotoxicity of these medications can become a significant consideration. The question of misdiagnosis of mood instability and off-label use occurring in personality disorders and substance abuse is also addressed. Psychotherapeutic interventions such as psychoeducation, family therapy, and cognitive behavioral therapy that support the treatment of bipolar disorder are described as a part of the deprescribing process and illustrated by case examples.
Deprescribing Benzodiazepines, Z-Drugs, and Stimulants
Authors: Gupta Swapnil , Miller Rebecca , Cahill John D.
Published: August 2019

This chapter addresses the considerations particular to deprescribing benzodiazepines and stimulant medications. Included are considerations around deprescribing those medications that a patient may be invested in taking either because the medications provide immediate relief or because they can improve occupational functioning in the short-term. Addiction and problem use (due to rewarding effects) of psychotropic medications are beyond the scope of this book and are amply addressed elsewhere. Addressed are psychoeducation needs, the acknowledgment of how much relief the medications bring, and the recognition of how severe and prolonged withdrawal symptoms can be. Accounts from patients experiencing prolonged withdrawal are included as well as suggestions around tapering speed and flexibility adapted to the patient’s response and supported by other measures such as cognitive behavioral therapy (CBT) for anxiety, CBT for insomnia, and connection with support groups.
Tracheal Narrowing and Tracheomalacia
Authors: Turakhia Aalok , Little Brent P. , Henry Travis S.
Published: August 2019

The etiologies of tracheal narrowing and stenosis are myriad. An important first step in formulating an imaging differential diagnosis is to divide tracheal narrowing into the following categories: neoplastic (benign and malignant), idiopathic, traumatic, inflammatory/infiltrative, and that caused by underlying pulmonary disease. Lesion location along the tracheobronchial wall, the presence or absence of calcifications, and evidence of extension through the tracheal wall are important characteristics that may help to further narrow the differential diagnosis. Post-intubation or post-traumatic tracheal stenosis is often treated by serial balloon dilatation, stenting, or segmental resection with re-anastamosis. Evaluation of both the length and degree of stenosis is important. Tracheomalacia is a dynamic process that is best evaluated with inspiratory and forced expiratory CT images to demonstrate tracheal collapse. Like other tracheal diseases, tracheomalacia may mimic asthma, or affected patient may present with non-specific symptoms. Significant respiratory dysfunction may result if tracheomalacia goes untreated. In the adult population, most tracheal tumors are malignant, and squamous cell carcinoma is the most common tumor detected.
Migration trends and dietary patterns in Sub-Saharan African adult immigrants: A comparative analysis of populations in France, the UK, and the USA
Authors: Ngoubene-Atioky Arlette J. , Case John , Tokplo Laetitia , Baur Christine
Published: August 2019

Sub-Saharan African (SSA) communities are part of a diverse and evolving African diaspora dispersed all over the world. Few studies have examined changes in eating habits of SSA communities who migrated in Western regions of the world. A critical review was conducted on the migration trends, dietary patterns, and dietary acculturation of SSA immigrants residing in the USA, the UK, and France. A comparative analysis revealed historical and contemporary influences of migration trends, the salience and significance of preserving traditional African diet post-migration, and the leading factors to and consequences of dietary acculturation. Limitations and recommendations for research and practice are described.
Relativistic polytrope from the collimation and acceleration profiles of the M87 jet at subparsec scales and thermodynamic evidence for the Blandford–Znajek mechanism
Authors: Sob’yanin (Денис Николаевич Собьянин) Denis Nikolaevich
Published: August 2019

Recent Very Long Baseline Interferometry observations of the relativistic jet in the M87 radio galaxy at 43 GHz show gradual relativistic acceleration of the plasma and suggest a linear dependence of Lorentz factor on jet radius at scales up to 8 marcsec (0.65 pc) from the core (2.5 marcsec in projection). General analysis of integrals of motion being unaltered along the jet and reflecting fundamental conservation laws shows that the above dependence implies a polytropic equation of state with index 4/3. The inferred value of the polytropic index appears independent of the exact nature of forces sustaining the transverse balance of the jet and indicates exact conservation of the longitudinal electric current and hence the existence of a stable internal electromagnetic structure at the scales under consideration. At this index the flow is hot and corresponds to relativistic thermodynamic motion of particles. Considerable weakening of the acceleration efficiency after 8 marcsec with the jet form being unchanged can be related to the plasma cooling, when the polytropic index becomes 5/3. Such a sharp change in the index without intermediate delay at 1.44 during cooling favours the existence of an electron–positron plasma and requires at least partial participation of the Blandford–Znajek mechanism in the launching of the M87 jet.
Hot, dense He iioutflows during the 2017 outburst of the X-ray transientSwift J1357.2−0933
Authors: Charles Phil , Matthews James H , Buckley David A H , Gandhi Poshak , Kotze Enrico , Paice John
Published: August 2019

Time-resolved SALT spectra of the short-period, dipping X-ray transient, Swift J1357.2−0933, during its 2017 outburst has revealed broad Balmer and He ii λ4686 absorption features, blueshifted by ∼600 km s−1. Remarkably these features are also variable on the ∼500 s dipping period, indicating their likely association with structure in the inner accretion disc. We interpret this as arising in a dense, hot (≳30 000 K) outflowing wind seen at very high inclination, and draw comparisons with other accretion disc corona sources. We argue against previous distance estimates of 1.5 kpc and favour a value ≳6 kpc, implying an X-ray luminosity LX ≳ 4 × 1036 erg s−1. Hence it is not a very faint X-ray transient. Our preliminary 1D Monte Carlo radiative transfer and photoionization calculations support this interpretation, as they imply a high intrinsic LX, a column density NH ≳ 1024 cm−2, and a low covering factor for the wind. Our study shows that Swift J1357.2−0933 is truly remarkable amongst the cohort of luminous, Galactic X-ray binaries, showing the first example of He  ii λ4686 absorption, the first (and only) variable dip period and is possibly the first black hole ‘accretion disc corona’ candidate.
Structure and DNA damage-dependent derepression mechanism for the XRE family member DG-DdrO
Authors: Lu Huizhi , Wang Liangyan , Li Shengjie , Pan Chaoming , Cheng Kaiying , Luo Yuxia , Xu Hong , Tian Bing , Zhao Ye , Hua Yuejin
Published: August 2019

DdrO is an XRE family transcription repressor that, in coordination with the metalloprotease PprI, is critical in the DNA damage response of Deinococcus species. Here, we report the crystal structure of Deinococcus geothermalis DdrO. Biochemical and structural studies revealed the conserved recognizing α-helix and extended dimeric interaction of the DdrO protein, which are essential for promoter DNA binding. Two conserved oppositely charged residues in the HTH motif of XRE family proteins form salt bridge interactions that are essential for promoter DNA binding. Notably, the C-terminal domain is stabilized by hydrophobic interactions of leucine/isoleucine-rich helices, which is critical for DdrO dimerization. Our findings suggest that DdrO is a novel XRE family transcriptional regulator that forms a distinctive dimer. The structure also provides insight into the mechanism of DdrO-PprI-mediated DNA damage response in Deinococcus.
Alexithymia Predicts Carotid Atherosclerosis, Vascular Events, and All-Cause Mortality in Human Immunodeficiency Virus-Infected Patients: An Italian Multisite Prospective Cohort Study
Authors: Vadini Francesco , Sozio Federica , Madeddu Giordano , De Socio Giuseppe , Maggi Paolo , Nunnari Giuseppe , Vichi Francesca , Di Stefano Paola , Tracanna Elisa , Polilli Ennio , Sciacca Antonina , Zizi Bernardetta , Lai Vincenzo , Bartolozzi Claudio , Flacco Maria Elena , Bonfanti Paolo , Santilli Francesca , Manzoli Lamberto , Parruti Giustino
Published: August 2019

Background

Psychological factors (PFs) are known predictors of cardiovascular disease (CVD) in many clinical settings, but data are lacking for human immunodeficiency virus (HIV) infection. We carried out a prospective study to evaluate (1) psychological predictors of preclinical and clinical vascular disease and (2) all-cause mortality (ACM) in HIV patients.

Methods

We conducted a cross-sectional analysis of baseline data to evaluate the predictors of carotid plaques (CPs) and a prospective analysis to explore predictors of vascular events (VEs) and ACM over 10 years. Human immunodeficiency virus patients monitored at the Infectious Disease Units of 6 Italian regions were consecutively enrolled. Traditional CVD risk factors, PFs (depressive symptoms, alexithymia, distress personality), and CPs were investigated. Vascular events and ACM after enrollment were censored at March 2018.

Results

A multicenter cohort of 712 HIV-positive patients (75.3% males, aged 46.1 ± 10.1 years) was recruited. One hundred seventy-five (31.6%) patients had CPs at baseline. At the cross-sectional analysis, alexithymia was independently associated with CPs (odds ratio, 4.93; 95% confidence interval [CI], 2.90–8.50; P < .001), after adjustment for sociodemographic, clinical, and psychological variables. After an average follow-up of 4.4 ± 2.4 years, 54 (7.6%) patients developed a VE, whereas 41 (5.68%) died. Age, current smoking, hypertension, and alexithymia (hazard ratio [HR], 3.66; 95% CI, 1.80–7.44; P < .001) were independent predictors of VE. Likewise, alexithymia was an independent predictor of ACM (HR, 3.93; 95% CI, 1.65–9.0; P = .002), regardless of other clinical predictors.

Conclusions

The present results validate our previous monocentric finding. Alexithymia may be an additional tool for the multifactorial assessment of cardiovascular risk in HIV.