bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of structural change in gonads of the divine dwarfgoby Eviota epiphanes as they sexually transition
Authors: Maxfield Jessica M. , Cole Kathleen S.
Published: December 2018

This study documents changes in gonadal structure for the serial hermaphrodite (or bidirectional sex changer) divine dwarfgoby Eviota epiphanes (family Gobiidae) as individuals transition in both directions. To evaluate transitional gonad morphology, individuals actively producing the same gamete type (oocytes or sperm) were set up into pairs and euthanised over a period of 14 days to get a time series of morphological changes during gonad transformation. Results from this study show that rapid changes in the gonad take place at a structural level as individuals change their reproductive function and gamete production. Changing from oocyte production (o‐phase) to sperm production (s‐phase) starts with the breakdown of vitellogenic oocytes (i.e., atresia) followed by the appearance and proliferation of spermatogenic tissue which, in most cases, was not previously visible. Changing from sperm production to oocyte production included the cessation of sperm production, a reduction in size and number of seminiferous lobules and the maturation of previtellogenic oocytes already present in the gonads. Experimental fish changed from oocyte production to sperm production more readily than from sperm production to oocyte production. The hypothesis that shifts in sexual function among serially hermaphroditic fish species have a similar cost in either direction is not supported in E. epiphanes.
University of Pittsburgh Medical Center Home Transitions Multidisciplinary Care Coordination Reduces Readmissions for Older Adults
Authors: Bellon Johanna E. , Bilderback Andrew , Ahuja‐Yende Namita S. , Wilson Cindy , Altieri Dunn Stefanie C. , Brodine Deborah , Boninger Michael L.
Published: December 2018

OBJECTIVES

To compare rates of 30‐ and 90‐day hospital readmissions and observation or emergency department (ED) returns of older adults using the University of Pittsburgh Medical Center (UPMC) Health Plan Home Transitions (HT) with those of Medicare fee‐for‐service (FFS) controls without HT.

DESIGN

Retrospective cohort study.

SETTING

Analysis of home health and hospital records from 8 UPMC hospitals in Allegheny County, Pennsylvania, from July 1, 2015, to April 30, 2017.

PARTICIPANTS

HT program participants (n=1,900) and controls (n=1,300).

INTERVENTION

HT is a care transitions program aimed at preventing readmission that identifies older adults at risk of readmission using a robust inclusion algorithm; deploys a multidisciplinary care team, including a nurse practitioner (NP), a social worker (SW), or both; and provides a multimodal service including personalized care planning, education, treatment, monitoring, and communication facilitation.

MEASUREMENT

We used multivariable logistic regression to determine the effects of HT on the odds of hospital readmission and observation or ED return, controlling for index admission participant characteristics and home health process measures.

RESULTS

The adjusted odds of 30‐day readmission was 0.31 (95% confidence interval (CI) = 0.11–0.87, P = .03) and of 90‐day readmission was 0.47 (95% CI=CI = 0.26–0.85, P = .01), for participants at medium risk of readmission in HT who received a team visit. The adjusted odds of 30‐day readmission was 0.29 (95% CI = 0.10–0.83, P = .02) for participants at high risk of readmission in HT who received a team visit. The adjusted odds of 30‐day observation or ED return was 1.90 (95% CI = 1.28–2.82, P = .001) for participants at medium risk of readmission in HT who received a team visit.

CONCLUSION

The HT program may be associated with lower odds of 30‐ and 90‐day hospital readmission and counterbalancing higher odds of observation or ED return. J Am Geriatr Soc 67:156–163, 2019.
Exclusion of Older Adults from Ongoing Clinical Trials on Low Back Pain: A Review of the WHO Trial Registry Database
Authors: Carvalho do Nascimento Paulo Roberto , Ferreira Manuela Loureiro , Poitras Stéphane , Bilodeau Martin
Published: December 2018

Background/Objectives

The burden of low back pain (LBP) is high, especially for older adults who experience a higher number of years living with a disability. However, this population is not being well represented in clinical trials (CTs). This study analyzed the International Clinical Trial Registry Platform (ICTRP) database from the World Health Organization to verify the future trend in the participation of older adults in registered CTs on LBP.

Design

We performed a cross‐sectional review of the ICTRP searching for prospective protocols planning interventions for LBP with registration dates from January 2015 through November 2018. From the protocols of the eligible studies, we extracted those planning to include older adults.

Results

A total of 167 protocols for CTs for LBP were planning to recruit participants older than 65 years. However, only five registries (2.99%; pooled sample = 169 participants) were designed to target participants specifically older than 65 years. The exclusion of older participants was not justified and imposed through an arbitrary upper‐age limit in 93.6% of the protocols. Most of the protocols are from single‐center studies, and a greater number are planned to be carried out in developed regions. Higher interest was in pharmacologic interventions, devices/technology, and physical rehabilitation.

Conclusion

Older adults with LBP will continue to be underinvestigated in CTs for LBP in the near future. In general, ongoing trials are small, planned in developed regions, and proposing pharmacologic interventions to deal with LBP. J Am Geriatr Soc 67:603–608, 2019.
Unripe peach (Prunus persica) extract ameliorates damage from UV irradiation and improved collagen XVIII expression in 3D skin model
Authors: Yonezawa Tomoko , Momota Ryusuke , Iwano Hideki , Zhao Steven , Hakozaki Tomohiro , Soh Chieko , Sawaki Shigetoyo , Toyama Kazumi , Oohashi Toshitaka
Published: December 2018

Introduction

Collagen type XVIII regulates cellular activities of adjacent cells at the dermal‐epidermal junction (DEJ). To investigate its possible changes during aging, we compared its mRNA levels and protein localization in skin samples from female participants aged 20‐70 years old. In addition, we evaluated the beneficial effects of unripe peach extracts in a 3D skin model.

Methods

Sun‐exposed or sun‐protected female skin samples were compared by DNA array or by immunohistochemistry for basement membrane components. To evaluate protective effects of fresh unripe peach extract, UV‐B irradiated human 3D skin models were incubated in the presence or absence of the extract, followed by measurements of mRNA levels by real‐time PCR, or by immunohistochemistry.

Results

In aged skin samples, COL18A1 mRNA levels were lower and the protein localization exhibited less intensive signal by anti‐collagen type XVIII immunostaining. As observed in the skin tissues, collagen type XVIII exists at the DEJ in the 3D skin model. Fresh unripe peach extract significantly improved mRNA levels and partially localizations of collagen type XVIII, suggesting that fresh unripe peach extract ameliorates DEJ damages caused by UV‐B irradiation.

Conclusion

Collagen type XVIII and fresh unripe peach extract can be promising protective cosmetic strategies against skin aging.
Clinical and echocardiography predictors of response to inhaled nitric oxide in hypoxic preterm neonates
Authors: Ahmed Mohamed Shalabi , Giesinger Regan E , Ibrahim Mohamed , Baczynski Michelle , Louis Deepak , McNamara Karl P , Jain Amish , Weisz Dany E , McNamara Patrick J
Published: December 2018

Aim

To evaluate the clinical and echocardiography modulators of treatment response in hypoxemic preterm infants exposed to inhaled nitric oxide (iNO).

Methods

In this multicentre retrospective study, clinical parameters, including oxygenation, ventilation and haemodynamics, were collected for preterm infants <36 weeks gestation before and 2 h after initiation of iNO for acute hypoxemia. Comprehensive echocardiography, performed near the time iNO initiation, was analysed by experts blind to the clinical course. Multiple logistic regression analysis was used to identify factors associated with iNO response as defined by a reduction in the fraction of inspired oxygen by >0.20.

Results

A total of 213 infants met eligibility criteria, of which 73 had echocardiography data available and formed the study cohort. Response to iNO was demonstrated in 56% of patients. Younger post‐natal age (odds ratio (OR) 0.94; 95% confidence interval (CI) 0.89, 0.99) and the presence of pulmonary hypertension (PH) (OR 4.47; 95% CI 1.23–11.9) were independently predictive of iNO response regardless of gestational age. Among neonates <72 h old with documented PH, iNO response was seen in 82%. The onset of a new diagnosis of severe (grade III/IV) intraventricular haemorrhage (IVH) after iNO treatment was seen in 6 of 40 patients <28 weeks' gestational age, with a greater frequency in responders (32 vs. 0%, P = 0.02).

Conclusions

Positive response to iNO is greatest in the first 3 days of life and in patients with echo‐confirmed PH, independent of gestational age. The association between critical illness, iNO administration and IVH in extremely premature infants may merit prospective delineation.
A polyphasic approach to the delimitation of diatom species: a case study for the genusPinnularia(Bacillariophyta)
Authors: Kollár Jan , Pinseel Eveline , Vanormelingen Pieter , Poulíčková Aloisie , Souffreau Caroline , Dvořák Petr , Vyverman Wim
Published: December 2018

Diatoms are one of the most abundant and arguably the most species‐rich group of protists. Diatom species delimitation has often been based exclusively on the recognition of morphological discontinuities without investigation of other lines of evidence. Even thoughDNAsequences and reproductive experiments have revealed several examples of (pseudo)cryptic diversity, our understanding of diatom species boundaries and diversity remains limited. The cosmopolitan pennate raphid diatom genusPinnulariarepresents one of the most taxon‐rich diatom genera. In this study, we focused on the delimitation of species in one of the major clades of the genus, thePinnularia subgibbagroup, based on 105 strains from a worldwide origin. We compared genetic distances between the sequences of seven molecular markers and selected the most variable pair, the mitochondrialcox1 and nuclear encodedLSU rDNA, to formulate a primary hypothesis on the species limits using three single‐locus automated species delimitation methods. We compared theDNA‐based primary hypotheses with morphology and with other available lines of evidence. The results indicate that our data set comprised 15 species of theP. subgibbagroup. The vast majority of these taxa have an uncertain taxonomic identity, suggesting that several may be unknown to science and/or members of (pseudo)cryptic species complexes within theP. subgibbagroup.
Role of soluble inflammatory mediators and different immune cell populations in early control of symptomatic acute hepatitis C virus infection
Authors: Hengst Julia , Klein Andreas L. , Lunemann Sebastian , Deterding Katja , Hardtke Svenja , Falk Christine S. , Manns Michael P. , Cornberg Markus , Schlaphoff Verena , Wedemeyer Heiner
Published: December 2018

The natural course of acute Hepatitis C Virus (aHCV) infection is highly heterogeneous, and only few biomarkers have been identified to reliably predict the outcome of infection. We analysed a large panel of soluble inflammatory mediators, immune cell frequencies and phenotypes using peripheral blood samples from 26 patients with symptomatic aHCV infection from a controlled randomized clinical trial (ISRCTN88729946, www.isrctn.com). We found that patients with a spontaneous early HCV control demonstrated a distinct expression pattern of various soluble immune mediators including IFNα and IL‐16. Immune cell phenotype and frequency differed between patients who cleared the viral infection early (n=13) and those who remained HCV RNA positive after 12 weeks of observation (n=13) with a reduced ratio of CD4+ T cells to NK cells in the non–early clearer. Further, correlation analyses of 50 cytokines and chemokines revealed more positive correlations in between the distinct cytokines, especially for IFNα and IL‐16, and between the cytokines and HCV RNA levels in spontaneous early clearer patients. Beyond that, in vitro stimulation of CD4+ T cells with IL‐16 reduced the susceptibility of these cells to killing by IFNα‐activated NK cells. These data indicate that the immune cell composition and cytokine pattern varies considerably in patients with symptomatic aHCV infection. NK cell–mediated killing of CD4+ T cells might affect early control of HCV infection.
Atrial fibrillation is highly prevalent yet undertreated in patients with biopsy‐proven nonalcoholic steatohepatitis
Authors: Whitsett Maureen , Wilcox Jane , Yang Amy , Zhao Lihui , Rinella Mary , VanWagner Lisa B.
Published: December 2018

Background & Aims

Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular disease. Atrial fibrillation is a prominent risk marker for underlying cardiovascular disease with a prevalence of 2% in patients <65 years old. Atrial fibrillation prevalence in NASH is unknown. We sought to assess the prevalence and impact of atrial fibrillation on healthcare utilization in NASH.

Methods

Patients were identified from a tertiary care centre Electronic Database from 2002 to 2015. International Classification of Diseases 9 (ICD9) codes identified comorbidities and atrial fibrillation. Descriptive statistics were used to compare characteristics between patients with NASH with and without atrial fibrillation.

Results

Of 9108 patients with ICD9 diagnosis of NASH, 215 (2.3%, mean age 57 years, 32% male) had biopsy‐proven NASH. Atrial fibrillation prevalence was 4.6%. Patients with NASH and atrial fibrillation had a higher prevalence of heart failure (54.5% vs 8.8%, P < 0.001) and cerebrovascular (27.3% vs 2.0%, P < 0.001) or vascular disease (54.5% vs 13.2%, P = 0.002), compared to NASH without atrial fibrillation. All patients with NASH and atrial fibrillation had a CHA2DS2VASc score ≥2 indicating high stroke risk and need for anticoagulation. Eight of 10 patients were eligible for anticoagulation and 5 of 8 (62.5%) received appropriate therapy.

Conclusion

Atrial fibrillation prevalence is two‐fold higher in patients with NASH compared to the general population. Patients with NASH have a high risk of stroke; however, many do not receive appropriate guideline‐directed therapy. Future studies are needed to identify whether guideline‐based management of atrial fibrillation in NASH reduces cardiovascular morbidity and mortality.
Periplasmic protein EipA determines envelope stress resistance and virulence in Brucella abortus
Authors: Herrou Julien , Willett Jonathan W. , Fiebig Aretha , Varesio Lydia M. , Czyż Daniel M. , Cheng Jason X. , Ultee Eveline , Briegel Ariane , Bigelow Lance , Babnigg Gyorgy , Kim Youngchang , Crosson Sean
Published: December 2018

Molecular components of the Brucella abortus cell envelope play a major role in its ability to infect, colonize and survive inside mammalian host cells. In this study, we have defined a role for a conserved gene of unknown function in B. abortus envelope stress resistance and infection. Expression of this gene, which we name eipA, is directly activated by the essential cell cycle regulator, CtrA. eipA encodes a soluble periplasmic protein that adopts an unusual eight‐stranded β‐barrel fold. Deletion of eipA attenuates replication and survival in macrophage and mouse infection models, and results in sensitivity to treatments that compromise the cell envelope integrity. Transposon disruption of genes required for LPS O‐polysaccharide biosynthesis is synthetically lethal with eipA deletion. This genetic connection between O‐polysaccharide and eipA is corroborated by our discovery that eipA is essential in Brucella ovis, a naturally rough species that harbors mutations in several genes required for O‐polysaccharide production. Conditional depletion of eipA expression in B. ovis results in a cell chaining phenotype, providing evidence that eipA directly or indirectly influences cell division in Brucella. We conclude that EipA is a molecular determinant of Brucella virulence that functions to maintain cell envelope integrity and influences cell division.
Fungicide resistance toward fludioxonil conferred by overexpression of the phosphatase gene MoPTP2 inMagnaporthe oryzae
Authors: Bohnert Stefan , Heck Larissa , Gruber Christoph , Neumann Hendrik , Distler Ute , Tenzer Stefan , Yemelin Alexander , Thines Eckhard , Jacob Stefan
Published: December 2018

The fungicide fludioxonil causes hyperactivation of the Hog1p MAPK within the high‐osmolarity glycerol signaling pathway essential for osmoregulation in pathogenic fungi. The molecular regulation of MoHog1p phosphorylation is not completely understood in pathogenic fungi. Thus, we identified and characterized the putative MoHog1p‐interacting phosphatase geneMoPTP2in the filamentous rice pathogenMagnaporthe oryzae. We found overexpression ofMoPTP2conferred fludioxonil resistance inM. oryzae, whereas the ‘loss of function’ mutantΔMoptp2was more susceptible toward the fungicide. Additionally, quantitative phosphoproteome profiling of MoHog1p phosphorylation revealed lower phosphorylation levels of MoHog1p in the MoPtp2p overexpression mutant compared to the wild‐type strain, whereas MoHog1p phosphorylation increased in theΔMoptp2mutant. Furthermore, we identified a set of MoHog1p‐dependent genes regulated by the MoPtp2p expression level. Our results indicate that the phosphatase MoPtp2p is involved in the regulation of MoHog1p phosphorylation and that overexpression of the geneMoPTP2is a novel molecular mechanism of fungicide resistance.
The UzcRS two‐component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators
Authors: Park Dan M. , Overton K. Wesley , Jiao Yongqin
Published: December 2018

The UzcRS two‐component system in Caulobacter crescentus mediates widespread transcriptional activation in response to the metals U, Zn and Cu. Unexpectedly, a screen for mutations that affected the activity of the UzcR‐regulated urcA promoter (PurcA) revealed four previously uncharacterized proteins whose inactivation led to metal‐independent induction of PurcA. Using molecular genetics and functional genomics, we find that these auxiliary regulators control PurcA expression by modulating the activity of UzcRS through distinct mechanisms. An ABC transporter with a periplasmic metallo‐aminopeptidase domain forms a sensory complex with UzcRS, antagonizing metal dependent stimulation by virtue of its ATPase and peptidase domains. Two MarR‐like transcription factors synergistically regulate UzcRS activity by repressing the expression of the membrane proteins UzcY and UzcZ, which stimulate UzcRS activity and enhance its sensitivity to a more environmentally relevant U/Zn/Cu concentration range. Additionally, the membrane protein UzcX, whose expression is positively regulated by UzcR, provides a mechanism of feedback inhibition within the UzcRS circuit. Collectively, these data suggest that UzcRS functions as the core‐signaling unit within a multicomponent signal transduction pathway that includes a diverse set of auxiliary regulators, providing further insight into the complexity of signaling networks.
Activation of immune receptor Rx1 triggers distinct immune responses culminating in cell death after 4 hours
Authors: Knip Marijn , Richard Manon M.S. , Oskam Lisa , van Engelen Hylco T.D. , Aalders Thomas , Takken Frank L.W.
Published: December 2018

Intracellular nucleotide‐binding leucine‐rich repeat (NLR)‐type immune receptors are a fundamental part of plant immune systems. As infection occurs at foci, activation of immune responses is typically non‐uniform and non‐synchronized, hampering the systematic dissection of their cellular effects and determining their phasing. We investigated the potato NLR Rx1 using the CESSNA (Controlled Expression of effectors for Synchronized and Systemic NLR Activation) platform. CESSNA‐mediated Potato virus X coat protein (CP) expression allowed the monitoring of Rx1‐mediated immune responses in a quantitative and reproducible manner. Rx1 was found to trigger a reactive oxygen species (ROS) burst and ion leakage within 1 h and a change in autofluorescence within 2 h after the induction of CP production. After 2 h, HIN1 expression was increased and single‐stranded DNA (ssDNA) damage and loss of cellular integrity became apparent, followed by double‐stranded DNA (dsDNA) damage after 3 h and increased PR‐1a, LOX, ERF1 and AOX1B expression and cell death at 4 h. Nuclear exclusion of Rx1 resulted in increased basal levels of ROS and permitted Rx1 activation by an Rx1‐breaking CP variant. In contrast, nuclear‐targeted Rx1 showed diminished basal ROS levels, and only avirulent CP could trigger a compromised ROS production. Both nuclear‐excluded and nuclear‐targeted Rx1 triggered a delayed ion leakage compared with non‐modified Rx1, suggesting that ion leakage and ROS production originate from distinct signalling pathways. This work offers novel insights into the influence of Rx1 localization on its activity, and the interplay between Rx1‐triggered processes.
The histone‐like protein HupB influences biofilm formation and virulence in Xanthomonas citri ssp. citri through the regulation of flagellar biosynthesis
Authors: Conforte Valeria P. , Malamud Florencia , Yaryura Pablo M. , Toum Terrones Laila , Torres Pablo S. , De Pino Verónica , Chazarreta Cristian N. , Gudesblat Gustavo E. , Castagnaro Atilio P. , R. Marano María , Vojnov Adrian A.
Published: December 2018

Citrus canker is an important disease of citrus, whose causal agent is the bacterium Xanthomonas citri ssp. citri (Xcc). In previous studies, we found a group of Xcc mutants, generated by the insertion of the Tn5 transposon, which showed impaired ability to attach to an abiotic substrate. One of these mutants carries the Tn5 insertion in hupB, a gene encoding a bacterial histone‐like protein, homologue to the β‐subunit of the Heat‐Unstable (HU) nucleoid protein of Escherichia coli. These types of protein are necessary to maintain the bacterial nucleoid organization and the global regulation of gene expression. Here, we characterized the influence of the mutation in hupB regarding Xcc biofilm formation and virulence. The mutant strain hupB was incapable of swimming in soft agar, whereas its complemented strain partially recovered this phenotype. Electron microscope imaging revealed that impaired motility of hupB was a consequence of the absence of the flagellum. Comparison of the expression of flagellar genes between the wild‐type strain and hupB showed that the mutant exhibited decreased expression of fliC (encoding flagellin). The hupB mutant also displayed reduced virulence compared with the wild‐type strain when they were used to infect Citrus lemon plants using different infection methods. Our results therefore show that the histone‐like protein HupB plays an essential role in the pathogenesis of Xcc through the regulation of biofilm formation and biosynthesis of the flagellum.
Association of klotho gene polymorphism and the regulation of calcium‐phosphate metabolism disorders in patients with end‐stage renal disease
Authors: Zeng Qing‐Ya , Xia Zhi‐Yin , Tong Yan‐Shan , Sun Liang , Mou Hong‐Bin , Chen Rui , Bi Guang‐Yu , Liu Chang‐Hua
Published: December 2018

Background

Klotho G‐395‐A gene polymorphism is associated with several diseases; however, its association with calcium‐phosphate metabolism disorders in end‐stage renal disease (ESRD) is unknown.

Methods

A total of 137 patients with ESRD and 80 healthy adults (control) were enrolled in the study. Patients with ESRD were divided into three subgroups: haemodialysis (A1, n = 52), peritoneal dialysis (A2, n = 30), and non‐dialysis (A3, n = 55). The klotho G‐395‐A genotype was detected by TaqMan PCR assay, and ELISA was used to detect the soluble klotho protein (sKL) and fibroblast growth factor (FGF23). Intact parathyroid hormone (iPTH) and other related clinical biochemical parameters were also analyzed for all subjects.

Results

(i) Three genotypes (GG, GA and AA) of KL G‐395A were detected, and a significant difference between the ESRD and control groups was observed, (ii) sKL was inversely associated with FGF23 in each subgroup and phosphate and positively associated with calcium in A1 and A3. FGF23 was positively associated with phosphate and inversely associated with calcium in each subgroup, (iii) a statistical difference in levels of sKL and FGF23 was observed between GG and AA, as well as between GA and AA. The expression of sKL was lowest and the level of FGF23 was highest in AA and (iv). GA + AA genotypes and FGF23 were risk factors and sKL might be protective factor of calcium‐phosphate metabolism disorders.

Conclusion

Soluble klotho protein and FGF23 were associated with the regulation of calcium and phosphate metabolism, and the A allele of the G‐395A klotho gene polymorphism could be a risk factor on calcium‐phosphate metabolism disorders in patients with ESRD.
Acute cellular rejection treatment outcomes stratified by Banff grade in pediatric kidney transplant
Authors: Chen Justin , Liverman Rochelle , Garro Rouba , Jernigan Stephanie , Travers Curtis , Winterberg Pamela D.
Published: December 2018

Introduction

There are limited data to guide optimal treatment strategies for acute cellular rejection (ACR) based on Banff grade for pediatric kidney transplant recipients. This report reviews a large pediatric transplant center's experience with ACR.

Materials and Methods

A retrospective analysis of pediatric kidney transplant recipients at our center from 2007 to 2014 was performed. Primary outcomes were incidence of graft failure and graft function one year following ACR based on Banff grade and treatment received.

Results

A total of 204 patients were reviewed, of which 65 received rejection treatment with either an oral steroid cycle (n = 16), intravenous steroid pulse (n = 28), or anti‐thymocyte globulin (rATG, n = 21). Overall, patients received rATG for treatment of more severe rejection associated with impaired graft function and as a group experienced statistically significant improvements in eGFR over the year following treatment, though most did not regain baseline graft function.

Discussion

Our data suggest that rATG is partially effective in treating ACR, but our study was underpowered to determine the effect of different treatments based on Banff grade. Since there is limited literature to guide clinical treatment of ACR in children, large transplant centers should collaborate to evaluate outcomes and establish evidence‐based practice.
Heart transplantation in two adolescents with Danon disease
Authors: Oren Daniel , Chau Peter , Manning Melanie , Kwong Joann , Kaufman Beth D. , Maeda Katsuhide , Rosenthal David N. , Hollander Seth A.
Published: December 2018

Danon disease (DD) is an X‐linked dominant disorder caused by a mutation in the lysosomal‐associated membrane protein‐2 (LAMP‐2) gene coding for the LAMP‐2 protein. We report two cases of successful heart transplantation (HT) in adolescent brothers with DD, including one who was bridged to HT for 34 days with a HeartWare left ventricular assist device. In both patients, the post‐transplant course was complicated by profound skeletal muscle weakness that resolved with corticosteroid withdrawal. These cases highlight that both HT and ventricular assist device support are feasible in patients with DD. Corticosteroid use may exacerbate skeletal myopathy, and therefore, steroid minimization may be warranted whenever possible.
Genetic diversity and molecular epidemiology of the T strain of Plum pox virus
Authors: Teber S. , Ceylan A. , Gürcan K. , Candresse T. , Ulubaş Serçe Ç. , Akbulut M. , Kaymak S. , Akbaş B.
Published: December 2018

Very limited information is available on the origin, diversity and evolution of Plum pox virus (PPV) ‘Turkey’ (T) strain. Phylogenetic analyses based on partial sequences of 421 isolates and complete genome sequences of 57 isolates, representing the geographical distribution of PPV‐T in Turkey, revealed the existence of several monophyletic and, in some cases, geographically limited groups within the PPV‐T strain (Ankara‐Konya1‐Kayseri, Ankara‐Balkan, Istanbul, Konya2 and Balkan). PPV‐T diversity (0.018%) was found to be greater than that of PPV strains D and Rec but lower than that of the M strain when including the newly described and divergent M‐Istanbul isolates, suggesting a long evolutionary history for PPV‐T. The European part of Turkey in the Balkans, close to Bulgaria where PPV was identified for the first time, appears as a likely centre of origin for PPV‐T isolates. The colonization of various parts of Turkey by diverse isolates from that region, followed by secondary local spread, is the most likely scenario for the diffusion of PPV‐T in Turkey.
Molecular identification of blast resistance genes in rice landraces from northeastern India
Authors: Susan A. , Yadav M. K. , Kar S. , Aravindan S. , Ngangkham U. , Raghu S. , Prabhukarthikeyan S. R. , Keerthana U. , Mukherjee S. C. , Salam J. L. , Adak T. , Banerjee A. , Rath P. C.
Published: December 2018

Rice blast disease caused by the fungus Magnaporthe oryzae is one of the most devastating diseases causing huge losses worldwide. In the present study, major blast resistance genes were investigated in landraces originating from northeastern India. Based on phenotypic evaluation, 288 landraces were classified into three distinct groups: resistant (75), moderately resistant (127) and susceptible (86). The genetic frequencies of the 18 major blast resistance genes were between 6.2% and 27.4%, with only two genotypes possessing a maximum of nine blast resistance genes. The cluster and population structure analysis grouped the landraces into two groups. Through principal coordinate analysis, the scatter plots partitioned the resistant and moderately resistant landraces into different groups. Analysis of molecular variance showed maximum (96%) diversity within populations and least (4%) diversity between populations. Association analysis identified six markers, CRG4_2, RM72, tk59‐2, pi21_79‐3, RM1233 and RM6648, that are significantly associated with blast disease and explained a phenotypic variance of 1.1–6.5%. The associated genes could be used in marker‐assisted rice breeding programmes for gene pyramiding to develop rice varietal resistance against blast disease. The present study represents a valuable blast resistance genetic resource that could be used for identification of new R genes, donors for blast resistance, and genomic studies.
Potassium deficiency aggravates yield loss in rice by restricting the translocation of non‐structural carbohydrates under Sarocladium oryzae infection condition
Authors: Zhang Jianglin , Lu Zhifeng , Pan Yonghui , Ren Tao , Cong Rihuan , Lu Jianwei , Li Xiaokun
Published: December 2018

Sheath rot disease (ShR) caused by Sarocladium oryzae (S. oryzae) infection is an emerging disease that causes severe yield loss by restricting the translocation of non‐structural carbohydrates (NSC). Potassium (K) nutrition plays a critical role in disease resistance and the exportation of NSC. However, the physiological mechanisms of K with respect to ShR have not been thoroughly elucidated to date. The objectives of this study were to reveal the mechanisms by which K increases ShR resistance by regulating NSC translocation of rice, therefore, a field experiment combined with an inoculation experiment was conducted. We demonstrate that ShR disease incidence and disease index decreased dramatically with an increasing K application. K deficiency sharply induced the accumulation of NSC in the flag leaf (FL) and flag leaf sheath (FLS) under S. oryzae infection condition, which reduced the contribution of transferred NSC to final yield. A permutational multivariate analysis showed that K deficiency had a greater (49.0%, P < 0.001) effect on the NSC content variation in FL than that of S. oryzae infection (15.0%, P < 0.001). S. oryzae infection dramatically increased the difference in apparent transferred mass of NSC and cell membrane injury of diseased organs between K‐deficient and K‐sufficient rice. Finally, we demonstrate that cell membrane injury was a limiting factor imposed by K deficiency, which restricts the export of NSC from source organs. This work highlights the importance of K in improving ShR resistance by regulating NSC translocation (particularly the stem NSC).
A CRISPR/Cas9 deletion into the phosphate transporter SlPHO1;1 reveals its role in phosphate nutrition of tomato seedlings
Authors: Zhao Panfeng , You Qiuye , Lei Mingguang
Published: December 2018

In vascular (Arabidopsis thaliana) and non‐vascular (Physcomitrella patens) plants, PHOSPHATE 1 (PHO1) homologs play important roles in the acquisition and transfer of phosphate. The tomato genome contains six genes (SlPHO1;1‐SlPHO1;6) homologous to AtPHO1. The six proteins have typical characteristics of the plant PHO1 family, such as the three Syg1/Pho81/XPRI (SPX) subdomains in the N‐terminal portion and one ERD1/XPR1/SYG1 (EXS) domain in the C‐terminal portion. Phylogenetic analysis revealed that the SlPHO1 family is subdivided into three clusters. A pairwise comparison indicated that SlPHO1;1 showed the highest level of sequence identity/similarity (67.39/76.21%) to AtPHO1. SlPHO1;1 deletion mutants induced by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 displayed typical phenotypes of Pi starvation, such as decreased shoot fresh weight and increased root fresh weight, therefore having a greater root‐to‐shoot ratio. Mutants also accumulated more anthocyanin and had more soluble Pi content in the root and less in the shoot. These results indicate that SlPHO1;1 plays an important role in Pi transport in the tomato at seedling stage.
Preservation of boar semen: An update
Authors: Pezo Felipe , Romero Fernando , Zambrano Fabiola , Sánchez Raúl Segundo
Published: December 2018

Contents

In the pork industry, artificial insemination and the storage of boar semen in liquid at 17°C are routinely applied to optimize the ejaculate and bring about rapid genetic changes that are reflected in the animal protein. Although the results are satisfactory, they are below what occurs with natural mating. It is currently possible to preserve boar semen with storage at 17°C and slow freezing, since to date there is only one study on vitrification, with negative results applicable only in the case of implementing an intracytoplasmic sperm injection. In both methods and due to the sensitivity of boar sperm to osmotic and temperature changes, there is a loss in the quality of the initial sample; however, slow freezing in boar semen has greater deleterious effects on the sample that are reflected in the pregnancy rates and number of live births. Therefore, only 1% of all inseminations are done with frozen semen. The aim of this review is to provide advances and results of studies conducted on the preservation of boar semen, delving more deeply into the critical points that each of the preservation techniques presents, including bacterial contamination, extender components, temperature, ice nucleation, use of additives in extenders and the main deleterious effects on sperm quality.
Socioeconomic Resource Environments in Biological and Alternative Family Care and Children's Cognitive Performance*
Authors: Font Sarah , Potter Marina H.
Published: December 2018

We examined social and economic resources in the environments of children involved with child protective services and their associations with children's cognitive performance. We used a national dataset of child protection investigations (children aged 6–16 at Wave 1). Using latent class analysis, we constructed profiles of the financial resources, parental education and employment, and family structure and size. We then examined within‐ and across‐time associations between resource environment profiles and children's math and reading scores and tested whether associations differed by family care type. Our latent class analysis identified four distinct family resource environments: educated middle class, single earner, large working class, and severely disadvantaged. Family resource environment profiles predicted current cognitive performance and changes in performance over time, but associations were more consistent for children in biological family care. Children who remain in home following maltreatment allegations may benefit from services that target social as well as economic resources.
Mitochondrial function modulates touch signalling in Arabidopsis thaliana
Authors: Xu Yue , Berkowitz Oliver , Narsai Reena , De Clercq Inge , Hooi Michelle , Bulone Vincent , Van Breusegem Frank , Whelan James , Wang Yan
Published: December 2018

Plants respond to short‐ and long‐term mechanical stimuli, via altered transcript abundance and growth respectively. Jasmonate, gibberellic acid and calcium have been implicated in mediating responses to mechanical stimuli. Previously it has been shown that the transcript abundance for the outer mitochondrial membrane protein of 66 kDa (OM66), is induced several fold after 30 min in response to touch. Therefore, the effect of mitochondrial function on the response to mechanical stimulation by touch at 30 min was investigated. Twenty‐five mutants targeting mitochondrial function or regulators revealed that all affected the touch transcriptome. Double and triple mutants revealed synergistic or antagonistic effects following the observed responses in the single mutants. Changes in the touch‐responsive transcriptome were localised, recurring with repeated rounds of stimulus. The gene expression kinetics after repeated touch were complex, displaying five distinct patterns. These transcriptomic responses were altered by some regulators of mitochondrial retrograde signalling, such as cyclic dependent protein kinase E1, a kinase protein in the mediator complex, and KIN10 (SnRK1 − sucrose non‐fermenting related protein kinase 1), revealing an overlap between the touch response and mitochondrial stress signalling and alternative mitochondrial metabolic pathways. Regulatory network analyses revealed touch‐induced stress responses and suppressed growth and biosynthetic processes. Interaction with the phytohormone signalling pathways indicated that ethylene and gibberellic acid had the greatest effect. Hormone measurements revealed that mutations of genes that encoded mitochondrial proteins altered hormone concentrations. Mitochondrial function modulates touch‐induced changes in gene expression directly through altered regulatory networks, and indirectly via altering hormonal levels.
Functional mapping of N deficiency‐induced response in wheat yield‐component traits by implementing high‐throughput phenotyping
Authors: Jiang Libo , Sun Lidan , Ye Meixia , Wang Jing , Wang Yaqun , Bogard Matthieu , Lacaze Xavier , Fournier Antoine , Beauchêne Katia , Gouache David , Wu Rongling
Published: December 2018

As overfertilization leads to environmental concerns and the cost of N fertilizer increases, the issue of how to select crop cultivars that can produce high yields on N‐deficient soils has become crucially important. However, little information is known about the genetic mechanisms by which crops respond to environmental changes induced by N signaling. Here, we dissected the genetic architecture of N‐induced phenotypic plasticity in bread wheat (Triticum aestivum L.) by integrating functional mapping and semiautomatic high‐throughput phenotyping data of yield‐related canopy architecture. We identified a set of quantitative trait loci (QTLs) that determined the pattern and magnitude of how wheat cultivars responded to low N stress from normal N supply throughout the wheat life cycle. This analysis highlighted the phenological landscape of genetic effects exerted by individual QTLs, as well as their interactions with N‐induced signals and with canopy measurement angles. This information may shed light on our mechanistic understanding of plant adaptation and provide valuable information for the breeding of N‐deficiency tolerant wheat varieties.
Comprehensive analysis of nuclear export of herpes simplex virus type 1 tegument proteins and their Epstein‐Barr virus orthologs
Authors: Funk Christina , Raschbichler Verena , Lieber Diana , Wetschky Jens , Arnold Eileen K. , Leimser Jacqueline , Biggel Michael , Friedel Caroline C. , Ruzsics Zsolt , Bailer Susanne M.
Published: December 2018

Morphogenesis of herpesviral virions is initiated in the nucleus but completed in the cytoplasm. Mature virions contain more than 25 tegument proteins many of which perform both nuclear and cytoplasmic functions suggesting they shuttle between these compartments. While nuclear import of herpesviral proteins was shown to be crucial for viral propagation, active nuclear export and its functional impact are still poorly understood. To systematically analyze nuclear export of tegument proteins present in virions of Herpes simplex virus type 1 (HSV1) and Epstein‐Barr virus (EBV), the Nuclear EXport Trapped by RAPamycin (NEX‐TRAP) was applied. Nine of the 22 investigated HSV1 tegument proteins including pUL4, pUL7, pUL11, pUL13, pUL21, pUL37d11, pUL47, pUL48 and pUS2 as well as 2 out of 6 EBV orthologs harbor nuclear export activity. A functional leucine‐rich nuclear export sequence (NES) recognized by the export factor CRM1/Xpo1 was identified in six of them. The comparison between experimental and bioinformatic data indicates that experimental validation of predicted NESs is required. Mutational analysis of the pUL48/VP16 NES revealed its importance for herpesviral propagation. Together our data suggest that nuclear export is an important feature of the herpesviral life cycle required to co‐ordinate nuclear and cytoplasmic processes.
Regulation of G protein‐coupled receptor signaling by plasma membrane organization and endocytosis
Authors: Weinberg Zara Y. , Puthenveedu Manojkumar A.
Published: December 2018

The trafficking of G protein coupled‐receptors (GPCRs) is one of the most exciting areas in cell biology because of recent advances demonstrating that GPCR signaling is spatially encoded. GPCRs, acting in a diverse array of physiological systems, can have differential signaling consequences depending on their subcellular localization. At the plasma membrane, GPCR organization could fine‐tune the initial stages of receptor signaling by determining the magnitude of signaling and the type of effectors to which receptors can couple. This organization is mediated by the lipid composition of the plasma membrane, receptor‐receptor interactions, and receptor interactions with intracellular scaffolding proteins. GPCR organization is subsequently changed by ligand binding and the regulated endocytosis of these receptors. Activated GPCRs can modulate the dynamics of their own endocytosis through changing clathrin‐coated pit dynamics, and through the scaffolding adaptor protein β‐arrestin. This endocytic regulation has signaling consequences, predominantly through modulation of the MAPK cascade. This review explores what is known about receptor sorting at the plasma membrane, protein partners that control receptor endocytosis, and the ways in which receptor sorting at the plasma membrane regulates downstream trafficking and signaling.
CLIP‐170 spatially modulates receptor tyrosine kinase recycling to coordinate cell migration
Authors: Zaoui Kossay , Duhamel Stephanie , Parachoniak Christine A. , Park Morag
Published: December 2018

Endocytic sorting of activated receptor tyrosine kinases (RTKs), alternating between recycling and degradative processes, controls signal duration, location and surface complement of RTKs. The microtubule (MT) plus‐end tracking proteins (+TIPs) play essential roles in various cellular activities including translocation of intracellular cargo. However, mechanisms through which RTKs recycle back to the plasma membrane following internalization in response to ligand remain poorly understood. We report that net outward‐directed movement of endocytic vesicles containing the hepatocyte growth factor (HGF) Met RTK, requires recruitment of the +TIP, CLIP‐170, as well as the association of CLIP‐170 to MT plus‐ends. In response to HGF, entry of Met into Rab4‐positive endosomes results in Golgi‐localized γ‐ear‐containing Arf‐binding protein 3 (GGA3) and CLIP‐170 recruitment to an activated Met RTK complex. We conclude that CLIP‐170 co‐ordinates the recycling and the transport of Met‐positive endocytic vesicles to plus‐ends of MTs towards the cell cortex, including the plasma membrane and the lamellipodia, thereby promoting cell migration.
Nucleated red blood cells as a novel indicator of CD34+ cell content in umbilical cord blood
Authors: Galel David , Crisostomo Clarence , Ortega Jennifer , Peters Kirstin , Neveu Sara , Davila Carolina , Barlow James
Published: December 2018

BACKGROUND

Umbilical cord blood (UCB) has become an important source of transplantable CD34+ hematopoietic progenitor cells. Cord blood banks (CBBs) can increase their efficiency by minimizing the processing of UCB units with low CD34+ content, which have a lower likelihood of transplant utilization. We sought to identify a readily available preprocessing metric that would correlate with CD34+ cell counts, without the cost of additional analysis.

STUDY DESIGN AND METHODS

Data were compiled for 131 UCB units processed at the regional CBB. Preprocessing hematologic metrics, including complete blood count and differential, were compared to postprocessing CD34+ cell quantities. The data were divided into six groups of varying preprocessing metrics, then compared for significant differences in postprocessing CD34+ cell quantities to develop a screening guidance.

RESULTS

UCB units with nucleated RBC (nRBC) content of 15% or greater were found to have a significant increase in CD34+ cell percentage (p < 0.00001) and total CD34+ cell content (p < 0.0001). Units with preprocessing total nucleated cell count (TNC) of ≥ 1.50 × 109 with nRBC content of 15% or greater, and for TNC ≥ of 2.00 × 109 with nRBC content less than15%, had a significant increase in CD34+ content (p < 0.05 and p < 0.001, respectively). Applied as a screening guideline, these units had an increase in mean CD34+ content from 6.24 × 106 to 9.27 × 106. Units originally in the bottom and top quartiles of CD34+ content constitute 5% and 53% of processed units meeting these TNC/nRBC criteria, respectively.

CONCLUSION

These screening criteria utilizing nRBC provides a guideline that public CBBs may use to increase their efficiency by minimizing the processing of UCB units with lower CD34+ cell content.