bluuebunny/crossref_metadata_2025 huggingface dataset:
Early detection of Y chromosome microdeletions in infertile men is helpful to guide clinical reproductive treatments in southwest of China
Authors: Liu Ting , Song Yu-Xin , Jiang Yong-Mei
Published: January 2019

The microdeletions of azoospermia factor (AZF) genes in Y chromosome are greatly associated with male infertility, which is also known as the second major genetic cause of spermatogenetic failure. Accumulating studies demonstrate that the different type of AZF microdeletions in patients reflect different clinical manifestations. Therefore, a better understanding of Y chromosome microdeletions might have broad implication for men health. In this study, we sought to determine the frequency and the character of different Y chromosome microdeletion types in infertile men in southwest of China.

In total, 1274 patients with azoospermia and oligozoospermia were recruited in southwest of China and screening for Y chromosome microdeletions in AZF regions by multiplex polymerase chain reaction.

The incidence of AZF microdeletions in southwest of China is 12.87%, which is higher than the national average. Further investigations unveiled that azoospermia factor c (AZFc) is the most frequent type of all the AZF microdeletions. Additionally, the number and also the quality of sperm in patients with AZFc microdeletion is decreasing with the age. Therefore, it is conceivable that the early testing for Y chromosome microdeletions in infertile men is crucial for fertility guidance.

The early detection of Y chromosome microdeletions in infertile men can not only clearly explain the etiology of oligzoospermia and azoospermia, but also help for the clinical management of both infertile man and his future male offspring.
Intramedullary bronchogenic cyst in the foramen magnum region accompanied with syringomyelia
Authors: Chen Fan , Marx Sascha , Zhang Chaochao , Cao Junguo , Yu Ying , Chen Dawei
Published: January 2019

Rationale:

Bronchogenic cysts refer to congenital anomalies derived from the primitive foregut. Spinal bronchogenic cysts are uncommon entities, and those occurring in the intramedullary sites are extremely rare. Bronchogenic cysts involving the foramen magnum region have only been described in 2 cases; however, intramedullary bronchogenic cysts with syringomyelia have not yet been reported.

Patient concerns:

A 46-year-old woman presented with a 6-month history of pain in the posterior neck region and a 1-month history of numbness in the upper extremities. Neurological examination revealed a loss of sensation in bilateral upper extremities and sensory dissociation. Magnetic resonance imaging (MRI) showed an intramedullary cystic lesion in the foramen magnum region and syringomyelia.

Diagnosis:

Histopathological findings were consistent with a bronchogenic cyst.

Interventions and outcomes:

A surgical resection of the cystic lesion was performed via a posterior midline approach. Under neurophysiological monitoring, the cyst was punctured, yielding gelatinous liquid. The dorsal part of the cystic wall was removed. One month postoperatively, the symptoms were resolved completely. Three months after operation, MRI showed no recurrence of the cyst and the syringomyelia disappeared.

Lessons:

Intramedullary bronchogenic cysts with syringomyelia are extremely rare. Preoperative identification is challenging and definitive diagnosis depends on histopathological evidence. Timely surgical resection should be highlighted.
Enhanced functional connectivity of the default mode network (DMN) in patients with spleen deficiency syndrome
Authors: Ning Yan-zhe , Wu Feng-zhi , Xue Song , Yin Dong-qing , Zhu Hong , Liu Jia , Jia Hong-xiao
Published: January 2019

Numerous studies had investigated the biological basis of spleen deficiency syndrome on gastrointestinal dysfunctions. However, little was known about neuropsychological mechanism of spleen deficiency syndrome. The default model network (DMN) plays an important role in cognitive processing. Our aim is to investigate the change of neuropsychological tests and DMN in patients with spleen deficiency syndrome.

Sixteen patients and 12 healthy subjects underwent functional magnetic resonance imaging examination, and 15 patients with spleen deficiency syndrome and 6 healthy subjects take part in the two neuropsychological tests.

Compared with healthy subjects, patients with spleen deficiency syndrome revealed significantly increased functional connectivity within DMN, and significantly higher in the scores of 2-FT (P = .002) and 3-FT (P = .014).

Our findings suggest that patients with spleen deficiency syndrome are associated with abnormal functional connectivity of DMN and part of neuropsychological tests, which provide new evidence in neuroimaging to support the notion of TCM that the spleen stores Yi and domains thoughts.
Spore powder of Ganoderma lucidum for Alzheimer's disease
Authors: Qin Li-Hong , Wang Chen , Qin Li-Wei , Liang Yan-Feng , Wang Guo-Hui
Published: January 2019

Background:

Previous studies have reported that spore powder of Ganoderma lucidum (SPGL) may be effective for the treatment of Alzheimer's disease (AD). However, its efficacy is still inconclusive. Thus, this systematic review will aim to assess its efficacy and safety for AD.

Methods:

We will search the electronic databases of Cochrane Central Register of Controlled Trials, EMBASE, MEDILINE, the Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database to assess the efficacy and safety of SPGL for patients with AD from their inceptions to the present. All case–control studies and randomized controlled trials will be considered for inclusion in this study. Two review authors will independently perform the study selection, data extraction, and risk of bias evaluation.

Results:

The primary outcome includes the cognitive status for patients. The secondary outcomes consist of the quality of life, AD symptoms, and adverse events.

Conclusions:

This systematic review will present the existing evidence for the efficacy and safety of SPGL for treating patients with AD.

Dissemination and ethics:

The results of this systematic review will be disseminated by through peer-reviewed journals. It does not needs ethic approval, because it does not involve individual patient data.

Systematic review registration:

PROSPERO CRD42019119426.
Factors related to the size of venous leg ulcers
Authors: Liu Xiaochun , Zheng Guofu , Ye Bo , Chen Weiqing , Xie Hailiang , Zhang Teng
Published: January 2019

Venous leg ulcers (VLUs) are an important health problem, and the size of ulcers often affects patient care, healing time, and quality of life. However, the risk factors associated with ulcer size have been rarely reported. The aim of this study was to establish the risk factors for the size of venous ulceration by analyzing the patient demographics and the results of duplex ultrasonography.

This study was an in-patient population-based cross-sectional study conducted at a single center during the period from 2013 to 2017. Men and women aged >18 years, who consecutively presented to our hospital with VLU, were included. According to the size of the ulcer, patients were divided into two groups, those with ulcers≤2 cm and those with ulcers >2 cm. Demographic, anthropometric, and clinical data were collected. For the analysis, univariate and multivariate logistic regressions were used.

A total of 232 patients with VLUs were admitted to our hospital from 2013 to 2017, including 117 patients (50.4%) with ulcer diameters ≤2 cm and 115 patients (49.6%) with ulcer diameters >2 cm. According to the results of the multivariate analysis, the ulcer duration (P = .001), the diameter of perforating veins (PVs) around the ulcers (P = .025), the reflux time of common femoral veins (CFVs) (P = .013), the reflux time of great saphenous veins (GSVs) (P = .021), and the reflux time of PVs around the ulcers (P = .001) were independent risk factors for VLUs.

These findings provide evidence that the size of VLU was significantly related to the ulcer duration, the diameter of PV around the ulcers, the CFV reflux time, the GSV reflux time, and the PV reflux time.
See-Hear-Feel-Speak
Authors: Samet Daniel , Luterman Sara
Published: January 2019

The presentation of children and adolescents with autism in the emergency department (ED) poses a unique set of challenges to clinicians and their teams, which have not yet been met. Children and adolescents with autism spectrum disorder (ASD) are more likely than their age and ethnically matched counterparts to visit both pediatric and general EDs and are more likely to use it for primary care complaints and dental care and to present for psychiatric concerns including suicidality. Despite the higher relative frequency, individuals with ASD demonstrate lower patient satisfaction, lower healthcare self-efficacy, and higher odds of unmet healthcare needs related to physical health, mental health, health maintenance, and vaccination. This can be ameliorated by simple strategies regarding communication, sensory and environmental modification, and distraction. After performing a literature review of existing evidence-based recommendations via PubMed as well as resources from autism advocacy and self-advocacy groups, we compiled a 4-step system: “See-Hear-Feel-Speak” an approach conducive to learning with the goal of enabling clinicians and their teams to facilitate patient-centered encounters with pediatric patients with ASD. The protocol meets the practicality requirements defined by published research.
Scientific Evidence for the Evaluation of Neurological Soft Signs as Atypical Neurodevelopment Markers in Childhood Neuropsychiatric Disorders
Authors: D’AGATI ELISA , PITZIANTI MARIABERNARDA , CURATOLO PAOLO , PASINI AUGUSTO
Published: January 2019

Motor dysfunction is commonly present in children with neurodevelopmental disorders. Developmental changes in voluntary control of motor skills include improvements in speed and motor coordination as well as reduced frequency of neurological soft signs (NSS) that are commonly observed in typically developing younger children. NSS are motor and sensory conditions that cannot be linked to specific cerebral lesions. The persistence of NSS into later childhood and adolescence is linked with an increased risk of psychiatric disorders. This finding gives support to the neurodevelopmental model of NSS in which minor neurological impairments may be viewed as potential signs of deviant brain development and might represent trait markers of vulnerability for neurodevelopmental disorders. Given that NSS are easily detectable, it is important that clinicians increase their knowledge of the clinical presentation and research implications of the relationship between NSS and childhood neurodevelopmental disorders. To the best of our knowledge, this is the first review article to give an updated overview of the current knowledge of NSS in the most common neuropsychiatric disorders of childhood/adolescence, such as attention-deficit/hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder, bipolar disorder, and first episode of psychosis. The article also presents key points for future research studies on this topic.
Is Ketamine the Future Clozapine for Depression? A Case Series and Literature Review on Maintenance Ketamine in Treatment-resistant Depression With Suicidal Behavior
Authors: CHAN LAI FONG , EU CHOON LENG , SOH SHEAN YIH , MANIAM THAMBU , SHAHIDII KADIR ZURI , CHONG BENEDICT TAK WAI , LOO JIANN LIN , SHARIP SHALISAH , WONG VINCENT CHOONG WAI , LOO TSUI HUEI , NG YIN PING , KAHN DAVID A.
Published: January 2019

Ketamine has shown effectiveness as a rapid-acting antidepressant with antisuicidal effects in terms of reduction of suicidal ideation in the short term. However, the evidence for long-term maintenance ketamine therapy for treatment-resistant depression (TRD) and suicidal behavior is limited. This case series (N=13) highlights the role of adjunctive serial maintenance ketamine infusions in restoring functionality in treatment-resistant unipolar and bipolar (mixed) depression with significant suicide risk and multiple comorbidities, including alcohol dependence. Two cases of TRD achieved functional remission with long-term maintenance ketamine treatment. The first case illustrates the potential synergistic interaction between ketamine and lamotrigine to achieve a sustained antidepressant response in the patient for 7 months. The second case may possibly be the longest reported case of maintenance ketamine therapy, with treatment continuing for 5 years to date. Ketamine treatment showed acute effectiveness in another 7 cases, especially in terms of reduction of suicidal ideation, albeit without significant long-term antidepressant effect. Factors that may contribute to lack of effectiveness of serial ketamine include inadequate mood stabilization in TRD in bipolar spectrum diagnoses, concomitant benzodiazepine use, complex comorbidities, and adverse effects such as significant hypertension and severe dissociation. Future systematic controlled studies are warranted to establish the efficacy and safety profile of long-term ketamine as maintenance therapy for TRD with suicidal behavior.
A New Therapeutic Group To Help Women With Borderline Personality Disorder and Their Infants
Authors: Sved Williams Anne E. , Yelland Chris , Hollamby Sharron , Wigley Maria , Aylward Paul
Published: January 2019

Objectives:

Few treatments have been described to treat the population of women with borderline personality structure who present in a dysregulated state with their infants. Therefore, a new treatment program was developed for this target group.

Methods:

A total of 45 women, who were identified clinically as meeting full or partial diagnostic criteria for borderline personality disorder (BPD) and having an infant younger than 3 years of age, were offered entry with their infant(s) into specialized dialectical behavior therapy groups, adapted to focus on parenting and the mother-infant relationship. Outcomes measured included maternal mood and anxiety, BPD functioning, parenting sense of competence, parental reflective functioning, and caregiver-infant interaction (CARE Index). Infants received high-quality child care while mothers attended each group, with dyadic reunions a further therapeutic focus each week.

Results:

A total of 29 women who met clinical or self-report measures for BPD and were offered group therapy began the program, 21 (72%) of whom completed the 24-week group program, with complete premeasures and postmeasures available for 20 dyads. Of the 20 women, 15 met full diagnostic criteria for BPD and 5 met partial criteria. Significant improvements were noted in maternal mood, with positive changes on 2 subscales of the Parental Reflective Function Questionnaire (prementalizing and increased curiosity in mental states); significant reductions in anxiety and BPD symptomatology were also observed. Only a medium effect size was found for parenting sense of competence, and in smaller numbers of participants as this scale was introduced later. It should particularly be noted that 15 dyads showed substantial change on the CARE Index, indicating improvement in dyadic relationships.

Conclusions:

This innovative adaptation of mother-infant dialectical behavior therapy showed promising improvements in maternal BPD symptoms and caregiver-infant relationships. Given that the feasibility and safety of this method have been demonstrated, a more methodologically rigorous trial with further refinements appears warranted to help this troubled cohort of patients.
Paranoid Syndrome as the First Sign of Central Neurocytoma: A Case Report
Authors: KARAKULA-JUCHNOWICZ HANNA , MORYLOWSKA-TOPOLSKA JUSTYNA , JUCHNOWICZ DARIUSZ , KORZENIOWSKA ALEKSANDRA , KRUKOW PAWEL , ROLA RADOSLAW
Published: January 2019

Central neurocytoma (CN), first described in 1982 by Hassoun and colleagues, is a rare tumor accounting for 0.25% to 0.5% of all tumors of the central nervous system. The tumor is a neoplasm of neuroepithelial origin, with intermediate malignancy (WHO grade II), detectable with both computed tomography and magnetic resonance imaging. Complete excision of the tumor gives favorable long-term results, with infrequent recurrences and/or metastases. Only 3 previous cases in which CN presented with co-occurring psychotic symptoms were found in the PubMed database. This report presents the case of a 27-year-old patient with paranoid syndrome without neurological symptoms, in whom magnetic resonance imaging confirmed a large intracranial tumor located predominantly in the right lateral ventricle and third ventricle reaching down to the hypothalamus. Resection of the tumor (histopathologically a CN) resulted in complete remission of the psychotic symptoms. This case supports the need for neuroimaging in all patients with first-episode psychosis because of the possibility of neurologically silent brain tumors. Quick diagnosis in such cases is crucial for the selection of treatment methods and prognosis.
Diagnosis and Use of Psychotherapy Among Children and Adolescents Prescribed Antipsychotics
Authors: VANBRONKHORST SARA B. , ROBERTS DANIEL E. , EDWARDS EVONNE M. , BLANKENSHIP KELLY
Published: January 2019

Objective:

To examine the diagnoses, demographics, and prevalence of psychotherapy use among children and adolescents prescribed antipsychotics by psychiatric providers in a community setting.

Methods:

Medical records from 1127 children aged 0 to 17 years who were prescribed antipsychotics in 2014-2015 at Pine Rest Christian Mental Health Services (PRCMHS) outpatient network were analyzed. Antipsychotics, diagnosis codes, demographics, and number of psychotherapy sessions during this time frame were analyzed using χ2 and logistic regression analyses.

Results:

During this year, 50.8% of the patients attended psychotherapy, and 35.6% attended 5 or more sessions of psychotherapy. The most prevalent primary diagnosis was bipolar disorder (37.1%), followed by attention-deficit/hyperactivity disorder (19.7%). Females being treated with antipsychotics were significantly more likely to attend psychotherapy than their male peers (55.7% vs. 47.9%, P=0.01). In the fully adjusted models, patients with diagnoses of bipolar disorder or disorders first diagnosed in infancy, childhood, or adolescence were less than half as likely to attend psychotherapy as patients with depressive disorders, with adjusted odds ratios of 0.41 and 0.42, respectively.

Conclusions:

Approximately half of the child and adolescent patients prescribed antipsychotics in this community sample did not attend psychotherapy, and 39% of the patients did not have a diagnosis of bipolar disorder, psychotic disorder, or autistic disorder.
Persistent Depressive Symptoms in a Population With High Levels of Occupational Stress: Trajectories Offer Insights Into Both Chronicity and Resilience
Authors: HYBELS CELIA F. , BLAZER DAN G. , PROESCHOLD-BELL RAE JEAN
Published: January 2019

Religious participation and spirituality are linked to good mental health. However, clergy may experience more depression than is observed in the general population, which may be due in part to high job strain. The objectives of this study were to identify distinct longitudinal trajectories of depressive symptoms in clergy and to identify variables associated with each course. The sample was 1172 clergy who were followed for up to 66 months. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-8), which was administered approximately every 6 months. Latent class trajectory analysis was conducted for group identification, and a 3-class trajectory model fit the data best. Class 1 (38% of the sample) had minimal or no depressive symptoms over time, class 2 (47%) had chronic mild symptoms, and class 3 (15%) had persistent moderate/severe symptoms. Occupational distress was significantly associated with trajectory class. The odds of being in either the chronic mild or the persistent moderate/severe depressive symptom class were significantly higher for those who were female, for those with fair/poor self-rated health, for those with more perceived financial or occupational stress, for those with lower levels of perceived emotional support, and/or for those with lower levels of spiritual well-being. The class exhibiting resilience to depressive symptoms had higher levels of perceived support and spiritual well-being as well as lower levels of perceived financial and occupational stress. A substantial percentage of clergy, and possibly people in similar helping occupations, may experience significant levels of depressive symptoms that do not remit over time. These individuals may benefit from treatments that address work-related coping.
Psychotherapy With Suicidal Patients Part 1: Expert Consensus Recommendations
Authors: PLAKUN ERIC M.
Published: January 2019

This column reviews and discusses recommendations made by individual experts and by expert panels for treating suicidal patients in psychotherapy. Therapies for suicidal patients that were considered for the extraction of shared elements include cognitive behavioral, psychodynamic, and integrated psychotherapies. There is a large amount of convergence among expert consensus recommendations for treating suicidal patients.
A Review of the Management of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis
Authors: Woolum Jordan A. , Bailey Abby M. , Baum Regan A. , Metts Elise L.
Published: January 2019

Stevens–Johnson syndrome and toxic epidermal necrolysis represent a spectrum of severe cutaneous adverse reactions that carry the potential for severe, long-term adverse effects, including death. Although medications are most commonly implicated in the development of these diseases, other factors, including infection and genetics, play a role. Management is generally supportive in nature and includes maintenance of the patient's airway, breathing, and circulation. Special disease considerations include the use of skin barrier management, unique infection prevention measures, and systemic immunomodulatory therapies.
Collaborative, Innovative Quality Improvement Activity: Development of Queensland Ambulance Service Stickers
Authors: Ding Mingshuang , Aitchison Stephen , Pink Edward , Brown Peter , Tan Victoria Ie Ching
Published: January 2019

This article discusses the implementation of 3 targeted interventions aimed at reducing infection rates in patients due to prolonged in situ intravascular catheters (IVCs) during their admission to the hospital. These IVCs are inserted by paramedics with Queensland Ambulance Service (QAS) in prehospital settings. The 3 interventions involved were the application of “QAS-IVC” stickers by QAS paramedics to indicate QAS-inserted IVCs, the implementation of mandatory IVC documentation during patient handover, and clinician engagement to provide patient education on IVC infection signs. Audits undertaken in wards reflected that the interventions were apparent and beneficial; this is evident from the limited number of patients having in-dwelling QAS-IVC and increased awareness among medical staff and patients alike. We, however, did not have comparative data to objectively quantify the success of the interventions implemented.
Cellulomonas rhizosphaerae sp. nov., a novel actinomycete isolated from soil
Authors: Tian Yuanyuan , Han Chuanyu , Hu Jiangmeihui , Zhao Junwei , Zhang Chen , Guo Xiaowei , Wang Xiangjing , Xiang Wensheng
Published: January 2019

A novel actinomycete, designated strain NEAU-TCZ24T, was isolated from soil and characterized using a polyphasic approach. The results of phylogenetic analysis based on the 16S rRNA gene sequence indicated that the organism should be assigned to the genus

Cellulomonas

and formed a stable clade with its closest relatives

Cellulomonas terrae

JCM 14899T (98.4 % 16S rRNA gene sequence similarity),

Cellulomonas xylanilytica

JCM 14281T (97.9 %) and

Cellulomonas humilata

JCM 11945T (97.7 %). The major menaquinones were identified as MK-9(H4) and MK-8(H4). The phospholipid profile was found to contain diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositolmannoside, a ninhydrin-positiveglycolipid, an unidentified phosphoglycolipid, an unidentified phospholipid and an unidentified lipid. The major fatty acids were identified as anteiso-C15 : 0, C18 : 1ω9c, C16 : 0 and anteiso-C17 : 0. Moreover, morphological and chemotaxonomic properties of NEAU-TCZ24T also confirmed the affiliation of the isolate to the genus

Cellulomonas

. However, multilocus sequence analysis based on five other house-keeping genes (gyrB, rpoB, recA, relA and atpD), DNA–DNA relatedness, physiological and biochemical data indicated that NEAU-TCZ24T could be distinguished from its closest relatives. Therefore, it is proposed that NEAU-TCZ24T represents a novel species of the genus

Cellulomonas

, for which the name

Cellulomonas
rhizosphaerae sp. nov. is proposed. The type strain is NEAU-TCZ24T (=CCTCC AA 2018042T=JCM 32383T).
Dyella monticola sp. nov. and Dyella psychrodurans sp. nov., isolated from monsoon evergreen broad-leaved forest soil of Dinghu Mountain, China
Authors: Zhou Xiang-yue , Gao Zeng-hong , Chen Mei-hong , Jian Mei-qi , Qiu Li-hong
Published: January 2019

Cells of bacterial strains 4 G-K06T and 4MSK11T, isolated from soil samples collected from monsoon evergreen broad-leaved forest of the Dinghushan Mountain (112° 31′ E 23° 10′ N), Guangdong Province, PR China, were Gram-stain-negative, aerobic, non-spore-forming, non-motile and rod-shaped. Strain 4 G-K06T grew at 10–37 °C, pH 3.5–7.5 and 0–3.5 % (w/v) NaCl; while 4MSK11T grew at 4–42 °C, pH 3.5–7.5 and 0–2.5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed strain 4 G-K06T formed a clade with

Dyella

flagellata

4 M-K16T, Dyella acidisoli 4M-Z03T,

Dyella

humi

DHG40T and

Dyella

nitratireducens

DHG59T, while strain 4MSK11T formed a clade with

Dyella

caseinilytica

DHOB09T and

Dyella

mobilis

DHON07T, both within the genus

Dyella

. The result of the partial atpD, gyrB and lepA gene sequence analysis supported the conclusion based on 16S rRNA gene sequence analysis, which showed that these two strains represent two novel species of

Dyella

. The average nucleotide identity and digital DNA–DNA hybridization value for the whole genomes were 75.0–79.0 and 20.3–22.6 % between strains 4 G-K06T, 4MSK11T and those described

Dyella

species with genome sequences; while the DNA–DNA hybridization rates between strains 4 G-K06T, 4MSK11T and closely related

Dyella

species (without genome sequence) were 29.5–41.8 %. The major cellular fatty acids of these two strains were iso-C15 : 0, iso-C16 : 0 and iso-C17 : 1
ω9c, while the major polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and several unidentified phospholipids and aminophospholipids. The only ubiquinone of these two strains was ubiquinone-8. The DNA G+C contents of 4 G-K06T and 4MSK11T were 60.4 and 61.3 mol%, respectively. On the basis of the evidence presented here, strains 4 G-K06T and 4MSK11T represent two novel species of the genus

Dyella

, for which the names

Dyella
monticola sp. nov. (type strain 4 G-K06T=LMG 30268T=GDMCC 1.1188T) and

Dyella
psychrodurans sp. nov. (type strain 4MSK11T=KCTC 62280T=GDMCC 1.1185T) are proposed.
Altererythrobacter insulae sp. nov., a lipolytic bacterium isolated from a tidal flat
Authors: Park Sooyeon , Park Ji-Min , Oh Tae-Kwang , Yoon Jung-Hoon
Published: January 2019

A lipolytic, Gram-stain-negative, aerobic, non-motile and coccoid, ovoid or rod-shaped bacterial strain, designated BPTF-M16T, was isolated from tidal flat sediment on the Yellow Sea in the Republic of Korea. Strain BPTF-M16T grew optimally at 30 °C and in the presence of 2.0–3.0 % (w/v) NaCl. A phylogenetic tree of 16S rRNA gene sequences showed that strain BPTF-M16T fell within the clade comprising the type strains of

Altererythrobacter

species. Strain BPTF-M16T exhibited 16S rRNA gene sequence similarity values of 98.0 and 97.1 % to the type strains of

Altererythrobacter

ishigakiensis

and

A

ltererythrobacter

marinus

, respectively, and of less than 97.0 % to the type strains of the other recognized species. Strain BPTF-M16T contained Q-10 as the predominant ubiquinone and C18 : 1
ω7c as the major fatty acid. The major polar lipids detected in strain BPTF-M16T were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingoglycolipid and one unidentified glycolipid. Mean DNA–DNA relatedness values of strain BPTF-M16T with the type strains of

A. ishigakiensis

and

A. marinus

were 22 and 13 %, respectively. The average nucleotide identity value between strain BPTF-M16T and the type strain of

A. ishigakiensis

was 76.80 %. Differential phenotypic properties, together with the phylogenetic and genetic data, revealed that strain BPTF-M16T is separated from recognized

Altererythrobacter

species. On the basis of the data presented here, strain BPTF-M16T is considered to represent a novel species of the genus

Altererythrobacter

, for which the name

Altererythrobacter
insulae sp. nov. is proposed. The type strain is BPTF-M16T (=KCTC 62421T=KACC 19609T=NBRC 113190T).
Dual forms of aging-related NADPH diaphorase neurodegeneration in the sacral spinal cord of aged non-human primates
Authors: Li Yinhua , Wei Zichun , Jia Yunge , Hou Wei , Wang Yu , Yu Shun , Shi Geming , Du Guanghui , Tan Huibing
Published: January 2019

We discovered two different anomalous NADPH diaphorase (NADPH-d) positive alterations, which were expressed as aging-related NADPH-d positive spheroidal bodies and megaloneurites specially distributed in the superficial dorsal horn, dorsal gray commissure (DGC), lateral collateral pathway (LCP) and sacral parasympathetic nucleus (SPN) in the aged monkeys’ sacral spinal cord, compared with the cervical, thoracic and lumbar segments. In the gracile nucleus of aged monkeys, only aging-related spheroidal bodies were observed and no megaloneurites occurred. The dense, abnormal NADPH-d positive megaloneurites, extremely different from regular NADPH-d positive fibers, were prominent in the sacral segments and occurred in extending from Lissauer’s tract (LT) through lamina I along the lateral boundary of the dorsal horn to the region of the SPN. Meanwhile, large diameter punctate NADPH-d activity occurred and scattered in the lateral white matter of the LCP and dorsal root entry zone (DREZ) at the same level of NADPH-d abnormality in the gray matters. Those dot-like NADPH-d alterations were examined by horizontal sectioning and indicated ascending or descending oriental fibers. These NADPH-d megaloneurites had the same composition as the punctate NADPH-d alterations and were co-localized with the VIP immunoreaction, while the ANBs did not coexist with the VIP immunoreaction. Both ANBs and megaloneurites provide consistent evidence that the anomalous neuritic alterations in the aged sacral spinal cord are referred to as a specialized aging marker in the pelvic visceral organs in non-human primates.
Coarse-grain simulations on NMR conformational ensembles highlight functional residues in proteins
Authors: Sacquin-Mora Sophie
Published: January 2019

Dynamics are a key feature of protein function, and this is especially true of gating residues, which occupy cavity or tunnel lining positions in the protein structure, and will reversibly switch between open and closed conformations in order to control the diffusion of small molecules within a protein’s internal matrix. Earlier work on globins and hydrogenases have shown that these gating residues can be detected using a multiscale scheme combining all atom classic molecular dynamics simulations and coarse grain calculations of the resulting conformational ensemble mechanical properties. Here we show that the structural variations observed in the conformational ensembles produced by NMR spectroscopy experiments are sufficient to induce noticeable mechanical changes in a protein, which in turn can be used to identify residues important for function and forming a mechanical nucleus in the protein core. This new approach, which combines experimental data and rapid coarse-grain calculations and no longer needs to resort to time-consuming all-atom simulations, was successfully applied to five different protein families.
The Role of Orexin-1 Receptor Signaling in Demand for the Opioid Fentanyl
Authors: Fragale Jennifer E. , Pantazis Caroline B. , James Morgan H. , Aston-Jones Gary
Published: January 2019

The orexin system is a potential treatment target for drug addiction. Orexin-1 receptor (OxR1) antagonism reduces demand for cocaine and remifentanil indicating that orexin-based therapies may reduce demand for many classes of abused drugs. However, pharmacokinetics vary greatly among opioids and it is unclear if OxR1 antagonism would reduce demand for all opioids, particularly ones with particularly high abuse liability. Here, we establish a behavioral economics (BE) procedure to assess the effects of OxR1 antagonism on demand for the highly abused opioid fentanyl. We also investigate the utility of our novel procedure in predicting OxR1 antagonism efficacy and relapse propensity. The OxR1 antagonist SB-334867 (SB) increased demand elasticity (α; decreased motivation) for fentanyl without affecting preferred consumption of fentanyl at null cost (Qo). Baseline α values predicted SB efficacy, such that SB was most effective at increasing demand elasticity in highly motivated rats. SB also attenuated cue-induced fentanyl seeking and baseline α values predicted the amount of reinstatement behavior. These results highlight the promise of the orexin system as a treatment target for opioid addiction and emphasize the usefulness of BE procedures in the study of opioid abuse.
The vagino-cervical microbiome as a woman’s life history
Authors: Jie Zhuye , Chen Chen , Hao Lilan , Li Fei , Tian Liu , Tong Xin , Song Liju , Cai Kaiye , Yu Xinlei , Li Ying , Rao Weiqiao , Liao Yunli , Zhou Dongsheng , Qiu Xuemei , Chen Xiaomin , Zi Jin , Liu Na , Zhang Wei , Liu Xiao , Xiao Liang , Xu Xun , Yang Huanming , Wang Jian , Hou Yong , Kristiansen Karsten , Jia Huijue
Published: January 2019

The gut microbiome has been the center of attention for human commensal microbiome studies. The vaginal microbiome is also densely populated with bacteria, viruses and fungi, and the presence of microorganisms beyond the cervix is increasingly reported in non-infectious conditions1–3. Due to the over 90% of human sequences in female reproductive tract samples3,4, metagenomic information has been very limited. 16S rRNA gene amplicon sequencing studies have identified community types in the vaginal microbiota, and observed its dynamic changes due to menstrual cycles and sexual behaviors in small cohorts5,6. Here we perform metagenomic shotgun sequencing on cervical samples from 516 women of reproductive age (more than 10-fold of the Human Microbiome Project (HMP)4), and dissect major factors, especially pregnancy and delivery histories and contraception methods on the microbiome composition. Features of other body sites, such as mood fluctuations and facial speckles could potentially be deduced from the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota in the female reproductive tract and imply disease susceptibilities that may be relieved by behavioural changes.
Cerebellar climbing fibers encode expected reward size
Authors: Larry Noga , Yarkoni Merav , Lixenberg Adi , Joshua Mati
Published: January 2019

Climbing fiber inputs to the cerebellum encode error signals that instruct learning. Recently, evidence has accumulated to suggest that the cerebellum is also involved in the processing of reward. To study how rewarding events are encoded, we recorded the activity of climbing fibers when monkeys were engaged in an eye movement task. At the beginning of each trial, the monkeys were cued the size of the reward that would be delivered upon successful completion of the trial. We found increased climbing fiber activity during cue presentation when information about reward size was first made available. Reward size did not modulate activity at reward delivery. These results indicate that climbing fibers encode the expected reward size and suggest a general role of the cerebellum in associative learning beyond error correction.
Highly efficient genome editing in primary bronchial epithelial cells establishes FOXJ1 as essential for ciliation in human airways
Authors: Rapiteanu Radu , Karagyozova Tina , Zimmermann Natalie , Wayne Gareth , Martufi Matteo , Belyaev Nikolai N , Singh Kuljit , Betts Joanna , Beinke Soren , Maratou Klio
Published: January 2019

The structure and composition of the bronchial epithelium is altered in respiratory diseases such as COPD and asthma, in which goblet cell hyperplasia and reduced numbers of ciliated cells impair mucociliary clearance. We describe a robust genome editing pipeline to interrogate modulators of primary human bronchial epithelial cell (HBEC) differentiation and function. By employing plasmid- and virus-free delivery of CRISPR/Cas9 to human airway basal cells we achieve highly efficient gene inactivation without the need for positive selection. Genome edited cells are differentiated at air liquid interface (ALI) into a pseudo-stratified epithelium. We focus on profiling ciliation using imaging cytometry coupled to confocal microscopy and immunohistochemistry. To our knowledge, this is the first study to describe highly efficient genome editing of ALI cultured primary HBECs. As proof of concept, we establish that inactivation of the gene encoding the transcription factor FOXJ1 in primary human airway basal cells precludes ciliation in ALI differentiated bronchial epithelia.
Genomics, evolutionary history and diagnostics of theAlternaria alternataspecies group including apple and Asian pear pathotypes
Authors: Armitage Andrew D. , Cockerton Helen M. , Sreenivasaprasad Surapareddy , Woodhall James , Lane Charles , Harrison Richard J. , Clarkson John P.
Published: January 2019

TheAlternariasectionalternaria(A. alternataspecies group) represents a diverse group of saprophytes, human allergens and plant pathogens.Alternariataxonomy has benefited from recent phylogenetic revision but the basis of differentiation between major phylogenetic clades within the group is not yet understood. Furthermore, genomic resources have been limited for the study of host-specific pathotypes. We report near complete genomes of the apple and Asian pear pathotypes as well as draft assemblies for a further 10 isolates representingAlternaria tenuissimaandAlternaria arborescenslineages. These assemblies provide the first insights into differentiation of these taxa as well as allowing the description of effector and non-effector profiles of apple and pear conditionally dispensable chromosomes (CDCs). We define the phylogenetic relationship between the isolates sequenced in this study and a further 23Alternariaspp. based on available genomes. We determine which of these genomes represent MAT1-1-1 or MAT1-2-1 idiomorphs and designate host-specific pathotypes. We show for the first time that the apple pathotype is polyphyletic, present in both theA. arborescensandA. tenuissimalineages. Furthermore, we profile a wider set of 89 isolates for both mating type idiomorphs and toxin gene markers. Mating-type distribution indicated that gene flow has occurred since the formation ofA. tenuissimaandA. arborescenslineages. We also developed primers designed toAMT14,a gene from the apple pathotype toxin gene cluster with homologs in all tested pathotypes. These primers allow identification and differentiation of apple, pear and strawberry pathotypes, providing new tools for pathogen diagnostics.
Suppressed Osteocyte Perilacunar / Canalicular Remodeling Plays a Causal Role in Osteoarthritis
Authors: Mazur Courtney M. , Woo Jonathon J. , Yee Cristal S. , Fields Aaron J. , Acevedo Claire , Bailey Karsyn N. , Fowler Tristan W. , Lotz Jeffrey C. , Dang Alexis , Kuo Alfred C. , Vail Thomas P. , Alliston Tamara
Published: January 2019

Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. To determine if PLR suppression plays a causal role in OA, we ablated the PLR enzyme MMP13 in osteocytes, while leaving chondrocytic MMP13 intact. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, this osteocyte-intrinsic PLR defect was sufficient to reduce cartilage proteoglycan content and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, osteocyte PLR is a critical regulator of cartilage homeostasis. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and identify the causal role of suppressed perilacunar/canalicular remodeling in osteoarthritis.
Illuminating the dark depths inside coral
Authors: Liu Chichi , Cheng Shuk Han , Lin Senjie
Published: January 2019

The ability to observe in situ 3D distribution and dynamics of endosymbionts in corals is crucial for gaining a mechanistic understanding of coral bleaching and reef degradation. Here, we report the development of a tissue clearing (TC)-coupled light sheet fluorescence microscopy (LSFM) method for 3D imaging of the coral holobiont at single-cell resolution. The initial applications have demonstrated the ability of this technique to provide high space-resolution quantitative information of endosymbiont abundance and distribution within corals. With specific fluorescent probes or assays, TC-LSFM also revealed spatial distribution and dynamics of physiological conditions (such as cell proliferation, apoptosis, and hypoxia response) in both corals and their endosymbionts. This tool is highly promising for in situ and in-depth data acquisition to illuminate coral symbiosis and health conditions in the changing marine environment, providing fundamental information for coral reef conservation and restoration.
Protocol-dependent differences in IC50 values measured in hERG assays occur in a predictable way and can be used to quantify state preference of drug binding
Authors: Lee William , Windley Monique J. , Perry Matthew D. , Vandenberg Jamie I. , Hill Adam P.
Published: January 2019

Current guidelines around preclinical screening for drug-induced arrhythmias require the measurement of the potency of block of Kv11.1 channels as a surrogate for risk. A shortcoming of this approach is that the measured IC50 of Kv11.1 block varies widely depending on the voltage protocol used in electrophysiological assays. In this study, we aimed to investigate the factors that that contribute to these differences and to identify whether it is possible to make predictions about protocol-dependent block that might facilitate comparison of potencies measured using different assays

Our data demonstrate that state preferential binding, together with drug binding kinetics and trapping, is an important determinant of the protocol-dependence of Kv11.1 block. We show for the first time that differences in IC50 measured between protocols occurs in a predictable way, such that machine learning algorithms trained using a selection of simple voltage protocols can indeed predict protocol-dependent potency. Furthermore, we also show that a drug’s preference for binding to the open versus the inactivated state of Kv11.1 can also be inferred from differences in IC50 measured between protocols.

Our work therefore identifies how state preferential drug binding is a major determinant of the protocol dependence of IC50 measured in preclinical Kv11.1 assays. It also provides a novel method for quantifying the state dependence of Kv11.1 drug binding that will facilitate the development of more complete models of drug binding to Kv11.1 and improve our understanding of proarrhythmic risk associated with compounds that block Kv11.1.
The systemin signaling cascade as derived from phosphorylation time courses under stimulation by systemin and its inactive Thr17Ala (A17) analog
Authors: Ahmad Fatima Haj , Wu Xuna , Stintzi Annick , Schaller Andreas , Schulze Waltraud X
Published: January 2019

Systemin is a small peptide with important functions in plant wound response signaling. Although transcriptional responses of systemin action are well described, the precise signaling cascades involved in its perception and signal transduction are poorly understood at the protein level. Here we use a phosphoproteomic profiling study involving stimulation time courses with systemin and its inactive analogon A17 to reconstruct a systemin-specific kinase/phosphatase signaling network. The time course analysis of systemin-induced phosphorylation patterns revealed early events at the plasma membrane, such dephosphorylation of H+-ATPase, rapid phosphorylation of NADPH-oxidase and Ca2+-ATPase. Later responses involved transient phosphorylation of small GTPases and vesicle trafficking proteins, as well as transcription factors. Based on a correlation analysis of systemin-specific phosphorylation profiles, we predict substrate candidates for 56 systemin specific kinases and 18 phosphatases. Among the kinases are several systemin-specific receptor kinases as well as kinases with downstream signaling functions, such as MAP-kinases. A regulatory circuit for plasma membrane H+-ATPase was predicted and confirmed by in-vitro activity assays. In this regulatory model we propose that upon systemin treatment, H+-ATPase LHA1 is rapidly de-phosphorylated at its C-terminal regulatory residue T955 by phosphatase PLL5, resulting in the alkalization of the growth medium within 2 minutes of systemin treatment. We further propose that the H+-ATPase LHA1 is re-activated by MAP-Kinase MPK2 later in the systemin response. MPK2 was identified with increased phosphorylation at its activating TEY-motif at 15 minutes of treatment and the predicted interaction with LHA1 was confirmed by in-vitro kinase assays. Our data set provides a valuable resource of proteomic events involved in the systemin signaling cascade with a focus on predictions of substrates to systemin-specific kinases and phosphatases.