bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Nutrient Restriction During Midgestation to Late Gestation on Maternal and Fetal Postruminal Carbohydrase Activities in Sheep
Authors: Trotta Ronald J , Vasquez-Hidalgo Manuel A , Vonnahme Kimberly A , Swanson Kendall C
Published: December 2019

To examine the effects of nutrient restriction during midgestation to late gestation on maternal and fetal digestive enzyme activities, 41 singleton ewes (48.3 ± 0.6 kg of BW) were randomly assigned to dietary treatments: 100% (control; CON; n = 20) or 60% of nutrient requirements (restricted; RES; n = 21) from day 50 until day 90 (midgestation). At day 90, 14 ewes (CON, n = 7; RES, n = 7) were euthanized. The remaining ewes were subjected to treatments of nutrient restriction or remained on a control diet from day 90 until day 130 (late gestation): CON-CON (n = 6), CON-RES (n = 7), RES-CON (n = 7), and RES-RES (n = 7) and were euthanized on day 130. The fetal and maternal pancreas and small intestines were weighed, subsampled, and assayed for digestive enzyme activity. One unit (U) of enzyme activity is equal to 1 µmol of product produced per minute for amylase, glucoamylase, lactase, and trypsin and 0.5 µmol of product produced per minute for maltase and isomaltase. Nutrient restriction during midgestation and late gestation decreased (P < 0.05) maternal pancreatic and small intestinal mass but did not affect fetal pancreatic or small intestinal mass. Maternal nutrient restriction during late gestation decreased (P = 0.03) fetal pancreatic trypsin content (U/pancreas) and tended to decrease (P < 0.08) fetal pancreatic trypsin concentration (U/g), specific activity (U/g protein), and content relative to BW (U/kg of BW). Nutrient restriction of gestating ewes decreased the total content of α-amylase (P = 0.04) and tended to decrease total content of trypsin (P = 0.06) and protein (P = 0.06) in the maternal pancreas on day 90. Nutrient restriction during midgestation on day 90 and during late gestation on day 130 decreased (P = 0.04) maternal pancreatic α-amylase-specific activity. Sucrase activity was undetected in the fetal and maternal small intestine. Nutrient restriction during late gestation increased (P = 0.01) maternal small intestinal maltase and lactase concentration and tended to increase (P = 0.06) isomaltase concentration. Realimentation during late gestation after nutrient restriction during midgestation increased lactase concentration (P = 0.04) and specific activity (P = 0.05) in the fetal small intestine. Fetal small intestinal maltase, isomaltase, and glucoamylase did not respond to maternal nutrient restriction. These data indicate that some maternal and fetal digestive enzyme activities may change in response to maternal nutrient restriction.
CLE-HAR1 Systemic Signaling and NIN-Mediated Local Signaling Suppress the Increased Rhizobial Infection in the daphne Mutant of Lotus japonicus
Authors: Yoro Emiko , Suzaki Takuya , Kawaguchi Masayoshi
Published: December 2019

Legumes survive in nitrogen-limited soil by forming a symbiosis with rhizobial bacteria. During root nodule symbiosis, legumes strictly control the development of their symbiotic organs, the nodules, in a process known as autoregulation of nodulation (AON). The study of hypernodulation mutants has elucidated the molecular basis of AON. Some hypernodulation mutants show an increase in rhizobial infection in addition to developmental alteration. However, the relationship between the AON and the regulation of rhizobial infection has not been clarified. We previously isolated daphne, a nodule inception (nin) allelic mutant, in Lotus japonicus. This mutant displayed dramatically increased rhizobial infection, suggesting the existence of NIN-mediated negative regulation of rhizobial infection. Here, we investigated whether the previously isolated components of AON, especially CLAVATA3/ESR (CLE)-RELATED-ROOT SIGNAL1 (CLE-RS1), CLE-RS2, and their putative receptor HYPERNODULATION AND ABERRANT ROOT FORMATION1 (HAR1), were able to suppress increased infection in the daphne mutant. The constitutive expression of LjCLE-RS1/2 strongly reduced the infection in the daphne mutant in a HAR1-dependent manner. Moreover, reciprocal grafting analysis showed that strong reduction of infection in daphne rootstock constitutively expressing LjCLE-RS1 was canceled by a scion of the har1 or klavier mutant, the genes responsible for encoding putative LjCLE-RS1 receptors. These data indicate that rhizobial infection is also systemically regulated by CLE-HAR1 signaling, a component of AON. In addition, the constitutive expression of NIN in daphne har1 double-mutant roots only partially reduced the rhizobial infection. Our findings indicate that the previously identified NIN-mediated negative regulation of infection involves unknown local signaling, as well as CLE-HAR1 long-distance signaling.
Superinfection Exclusion by p28 of Turnip Crinkle Virus Is Separable from Its Replication Function
Authors: Guo Qin , Zhang Shaoyan , Sun Rong , Yao Xiaolong , Zhang Xiao-Feng , Tatineni Satyanarayana , Meulia Tea , Qu Feng
Published: December 2019

We recently reported that the p28 auxiliary replication protein encoded by turnip crinkle virus (TCV) is also responsible for eliciting superinfection exclusion (SIE) against superinfecting TCV. However, it remains unresolved whether the replication function of p28 could be separated from its ability to elicit SIE. Here, we report the identification of two single amino acid mutations that decouple these two functions. Using an Agrobacterium infiltration-based delivery system, we transiently expressed a series of p28 deletion and point mutants, and tested their ability to elicit SIE against a cointroduced TCV replicon. We found that substituting alanine (A) for valine (V) and phenylalanine (F) at p28 positions 181 and 182, respectively, modestly compromised SIE in transiently expressed p28 derivatives. Upon incorporation into TCV replicons, V181A and F182A decoupled TCV replication and SIE diametrically. Although V181A impaired SIE without detectably compromising replication, F182A abolished TCV replication but had no effect on SIE once the replication of the defective replicon was restored through complementation. Both mutations diminished accumulation of p28 protein, suggesting that p28 must reach a concentration threshold in order to elicit a strong SIE. Importantly, the severe reduction of F182A protein levels correlated with a dramatic loss in the number of intracellular p28 foci formed by p28–p28 interactions. Together, these findings not only decouple the replication and SIE functions of p28 but also unveil a concentration dependence for p28 coalescence and SIE elicitation. These data further highlight the role of p28 multimerization in driving the exclusion of secondary TCV infections.
A curious case of colitis
Authors: Goriawala Alifiya , Easson Alexandra
Published: December 2019

Segmental colitis associated with diverticulosis (SCAD) is a rare variant of chronic colitis that is limited to segments of the left colon that harbor diverticula. Histologically, SCAD is known to mimic chronic idiopathic inflammatory bowel disease. Patients usually present with hematochezia and cramping abdominal pain; SCAD often resolves spontaneously without treatment, or completely after a limited course of therapy. Due to the histologic overlap with ulcerative colitis and occasional Crohn colitis, the implications of an inaccurate diagnosis are significant.
Improving health disparities in PA practices
Authors: Zuber Kim , McCall Timothy C. , Bruessow Diane , Devine Patricia J. , Straker Howard O.
Published: December 2019

Objective:

To assess a quality improvement initiative designed to highlight awareness of health disparities and improve healthcare practices among participants.

Methods:

Data were collected from 102 clinically practicing PAs over a 2-year timespan via the quality improvement initiative Outside the Box: Reducing Health Disparities. As part of the program, participants reviewed 10 random charts in their practice, documenting how they identified and/or managed common health disparities. Then, participants reviewed the educational materials provided and implemented practice-specific interventions. Thirty days after the initial review, a second random review of charts was executed.

Results:

Postintervention results showed statistically significant moderate- to large-sized quality improvement across most categories.

Conclusions:

This study demonstrates that Outside the Box participation was associated with practice quality improvements among participants in several domains that are known to experience health disparities. Results suggest that increasing awareness of ideal professional behaviors can result in quality improvements in practices.
Sport specialization in young athletes
Authors: Parker L. Taylor , LaBotz Michele
Published: December 2019

Many young athletes are pursuing high-intensity training and choosing to specialize in a single sport before high school. However, a growing body of literature suggests that this approach places children and adolescents at increased risk for physical and mental harm, and does not confer the desired benefit in the development of sport-specific skills. This article reviews concerns associated with early sport specialization, outlines principles of developmentally appropriate physical activity and athletic development, and provides practical guidance and resources to assist clinicians in counseling young athletes and their families.
First Drug Approved for Rare Lung Disease
Authors: Aschenbrenner Diane S.
Published: December 2019

Nintedanib (Ofev) is the first drug approved for the treatment of SSc-ILD, a rare interstitial lung disease associated with systemic sclerosis or scleroderma. This is a new indication for nintedanib, which was previously approved for idiopathic pulmonary fibrosis.
CE: Assessing and Managing Spiritual Distress in Cancer Survivorship
Authors: Nolan Timiya S. , Browning Kristine , Vo Jacqueline B. , Meadows Rachel J. , Paxton Raheem J.
Published: December 2019

More than 67% of people diagnosed with cancer in the United States are alive five years after receiving the diagnosis; but even if they are cancer free, the effects of the disease and its treatment will remain with them for the rest of their lives. Distress, which can be of a psychological, social, physical, or spiritual nature, is common among cancer survivors. Spiritual distress is a broad concept that is not necessarily associated with any specific religious beliefs, practices, or affiliations. Both religious and nonreligious people may have a strong sense of spirituality and may experience spiritual distress at various points throughout cancer survivorship. But clinicians often neglect to explore the spiritual components of distress, and despite the well-established association between spiritual well-being and quality of life, few of the instruments designed to assess the care needs of cancer survivors address spiritual needs. Through a composite clinical case, this article illustrates how nurses can incorporate into practice evidence-based recommendations for assessing and managing spiritual distress in cancer survivors.
Superior Stability and Compression Across Complex Peripheral Meniscal Tears: An Inside Out Technique
Authors: Patel Nimesh G. , Napier Richard J. , Walmsley Katie , Mandalia Vipul
Published: December 2019

Meniscal tear is the most common knee pathology. There are benefits to repairing and preserving the meniscus with regards to function and chondroprotection. Historically, reported failure rates have been unclear and are potentially due to technical aspects of the repair. Providing even compression across a meniscal tear provides the best stability. This, along with a good blood supply leads to the successful healing of the meniscus. Our technique utilizes an inside-out approach, achieving circumferential compression across the meniscal tear, thus providing better stability and low failure rates.
Role of dihydroceramides in the progression of acute-on-chronic liver failure in rats
Authors: Li Fang-Fang , Liu Ning , Liu Wei , Li Mei , Zhang Fan , Dong Zhen , Zhang Jin-Lan , Sun Hua
Published: December 2019

Background

Previously, dihydroceramide (d18:0/24:0) (dhCer (d18:0/24:0)) was reported to be a potential biomarker for acute-on-chronic liver failure (ACLF) prognosis. In this study, we further explored the role of dhCer (d18:0/24:0) in the progression of ACLF to validate the biomarker using ACLF rat model.

Methods

ACLF rats were sacrificed at 4 and 8 h post-D-galactosamine (D-gal)/lipopolysaccharide (LPS) administration to investigate the liver biochemical markers, prothrombin time and liver histopathology. Change in dhCer and other sphingolipids levels were investigated by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Rats were treated with N-(4-hydroxyphenyl) retinamide (4-HPR) to examine the mortality rate and its role in improving ACLF.

Results

LPS/D-gal administration resulted in significant elevation in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Prothrombin time was prolonged and histopathological examination showed abnormality. HPLC-MS/MS results showed total dhCer levels in ACLF group (64.10 ± 8.90 pmol/100 μL, 64.22 ± 6.78 pmol/100 μL for 4 and 8 h, respectively) were decreased significantly compared with control group (121.61 ± 23.09 pmol/100 μL) (P < 0.05). In particular, dhCer (d18:0/24:0), dhCer (d18:0/20:0), and dhCer (d18:0/22:0) levels were decreased. Treatment with 4-HPR significantly increased the levels of dhCers, including dhCer (d18:0/24:0) compared with ACLF group, for the level of dhCer (d18:0/24:0) in 4-HPR group was 20.10 ± 8.60 pmol/100 μL and the level of dhCer (d18:0/24:0) in ACLF group was 9.74 ± 2.99 pmol/100 μL (P < 0.05). This was associated with reduced mortality rate and prolonged survival time. The ALT and AST in 4-HPR group were significantly decreased compared with ACLF group. The prothrombin time of 4-HPR group (41.49 s) was significantly lower than the prothrombin time of ACLF group (57.96 s) (P < 0.05). 4-HPR also decreased plasma ammonia levels slightly, as the plasma ammonia levels in 4-HPR group and ACLF group were 207.37 ± 60.43, 209.15 ± 60.43 μmol/L, respectively. Further, 4-HPR treatment improved histopathological parameters.

Conclusions

DhCer, especially dhCer (d18:0/24:0), is involved in the progression of ACLF. Increasing the levels of dhCer can reduce the mortality rate of ACLF rats and alleviate liver injury.
Novel EIF5A-USP6 Gene Fusion in Nodular Fasciitis Associated With Unusual Pathologic Features: A Report of a Case and Review of the Literature
Authors: Lenz Jiri , Michal Michael , Svajdler Marian , Ptakova Nikola , Lenz David , Konecna Petra , Kavka Miroslav
Published: December 2019

Nodular fasciitis (NF) is a benign self-limiting soft tissue lesion that has long been considered a reactive process. Recently, however, the USP6 gene rearrangement has been discovered, and the neoplastic nature of this tumor was suggested. Since then, many fusion partners of the USP6 gene have been reported, with the MYH9 gene as the most common. In this article, we describe a case of NF with a novel EIF5A-USP6 gene fusion associated with unusual pathological features. A 41-year-old healthy woman with a painful, rapidly growing subcutaneous mass on the left forearm with a size of 0.8 cm is presented. A soft tissue fragment measuring 1 cm was surgically excised. Owing to positive surgical margins, re-excision was performed, yielding another 2-cm fragment. The lesion was extensively histologically investigated. Immunohistochemical and molecular–genetic analysis, namely fluorescence in situ hybridization, next-generation sequencing, and reverse transcriptase-polymerase chain reaction, were also performed. Histology revealed a dermally located, mitotically active myofibroblastic proliferation with myxoid areas that ulcerated the overlying epidermis. One atypical mitotic figure was also found. The lesion showed positive immunohistochemical staining with smooth muscle actin, whereas S100 protein and CD34 stains were negative. Using fluorescence in situ hybridization, the USP6 gene rearrangement was detected and subsequent analysis using the Archer fusionPlex Sarcoma kit revealed a novel EIF5A-USP6 gene fusion. In the appropriate clinicopathological context, the detection of USP6 gene rearrangement is extremely useful when diagnosing NF, significantly reducing the risk of misdiagnosis and inappropriate overtreatment.
Circulating Complement C3-Alpha Chain Levels Predict Survival of Septic Shock Patients
Authors: Cheng Tzu Hsuan , Puskarich Michael , Li Xiang , Fang Zhou , Xu Fou , Chen Yong , Jiang Xian-Cheng , Worah Samrat , Jones Alan E. , Zhang Ming
Published: December 2019

Background:

Circulating complement C3 fragments released during septic shock might contribute to the development of complications such as profound hypotension and disseminated intravascular coagulation. The role of C3 in the course of septic shock varies in the literature, possibly because circulating C3 exists in different forms indistinguishable via traditional ELISA-based methods. We sought to test the relationship between C3 forms, measured by Western blotting with its associated protein size differentiation feature, and clinical outcomes.

Methods:

Secondary analysis of two prospective cohorts of patients with septic shock: a discovery cohort of 24 patents and a validation cohort of 181 patients. C3 levels were measured by Western blotting in both cohorts using blood obtained at enrollment. Differences between survivors and non-survivors were compared, and the independent prognostic values of C3 forms were assessed.

Results:

In both cohorts there were significantly lower levels of the C3-alpha chain in non-survivors than in survivors, and persisted after controlling for sequential organ failure assessment score. Area under the receiver operating characteristics to predict survival was 0.65 (95% confidence interval: 0.56–0.75). At a best cutoff value (Youden) of 970.6 μg/mL, the test demonstrated a sensitivity of 68.5% and specificity of 61.5%. At this cutoff point, Kaplan–Meier survival analysis showed that patients with lower levels of C3-alpha chain had significantly lower survival than those with higher levels (P < 0.001).

Conclusion:

Circulating C3-alpha chain levels is a significant independent predictor of survival in septic shock patients.
Endotoxin Removal in Septic Shock with the Alteco LPS Adsorber Was Safe But Showed no Benefit Compared to Placebo in the Double-Blind Randomized Controlled Trial—the Asset Study
Authors: Lipcsey Miklos , Tenhunen Jyrki , Pischke Soeren E. , Kuitunen Anne , Flaatten Hans , De Geer Lina , Sjölin Jan , Frithiof Robert , Chew Michelle S. , Bendel Stepani , Kawati Rafael , Larsson Anders , Mollnes Tom Eirik , Tønnessen Tor Inge , Rubertsson Sten
Published: December 2019

Purpose:

Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco LPS Adsorber for LPS removal in early gram-negative septic shock was feasible and safe. Also, effects on endotoxin level, inflammatory response, and organ function were assessed.

Methods:

A pilot, double-blinded, randomized, Phase IIa, feasibility clinical investigation was undertaken in six Scandinavian intensive care units aiming to allocate 32 septic shock patients with abdominal or urogenital focus on LPS Adsorber therapy or a Sham Adsorber, therapy without active LPS binding. The study treatment was initiated within 12 h of inclusion and given for 6 h daily on first 2 days. LPS was measured in all patients.

Results:

The investigation was terminated after 527 days with eight patients included in the LPS Adsorber group and seven in the Sham group. Twenty-one adverse effects, judged not to be related to the device, were reported in three patients in the LPS Adsorber group and two in the Sham group. Two patients in the Sham group and no patients in the LPS Adsorber group died within 28 days. Plasma LPS levels were low without groups differences during or after adsorber therapy. The changes in inflammatory markers and organ function were similar in the groups.

Conclusions:

In a small cohort of patients with presumed gram-negative septic shock, levels of circulating endotoxin were low and no adverse effects within 28 days after LPS adsorber-treatment were observed. No benefit compared with a sham device was seen when using a LPS adsorber in addition to standard care.

Trial registration:

Clinicaltrials.gov NCT02335723. Registered: November 28, 2014.
Machine learning suggests polygenic contribution to cognitive dysfunction in amyotrophic lateral sclerosis
Authors: Placek Katerina , Benatar Michael , Wuu Joanne , Rampersaud Evadnie , Hennessy Laura , Van Deerlin Vivianna M. , Grossman Murray , Irwin David J. , Elman Lauren , McCluskey Leo , Quinn Colin , Granit Volkan , Statland Jeffrey M. , Burns Ted M. , Ravits John , Swenson Andrea , Katz Jon , Pioro Erik , Jackson Carlayne , Caress James , So Yuen , Maiser Samuel , Walk David , Lee Edward B. , Trojanowski John Q. , Cook Philip , Gee James , Sha Jin , Naj Adam C. , Rademakers Rosa ,   The CReATe Consortium, Chen Wenan , Wu Gang , Taylor J. Paul , McMillan Corey T.
Published: December 2019

Amyotrophic lateral sclerosis (ALS) is a multi-system disease characterized primarily by progressive muscle weakness. Cognitive dysfunction is commonly observed in patients, however factors influencing risk for cognitive dysfunction remain elusive. Using sparse canonical correlation analysis (sCCA), an unsupervised machine-learning technique, we observed that single nucleotide polymorphisms collectively associate with baseline cognitive performance in a large ALS patient cohort (N=327) from the multicenter Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium. We demonstrate that a polygenic risk score derived using sCCA relates to longitudinal cognitive decline in the same cohort, and also to in vivo cortical thinning in the orbital frontal cortex, anterior cingulate cortex, lateral temporal cortex, premotor cortex, and hippocampus (N=90) as well as post mortem motor cortical neuronal loss (N=87) in independent ALS cohorts from the University of Pennsylvania Integrated Neurodegenerative Disease Biobank. Our findings suggest that common genetic polymorphisms may exert a polygenic contribution to the risk of cortical disease vulnerability and cognitive dysfunction in ALS.
Crystal structure of a human plasma membrane phospholipid flippase
Authors: Nakanishi Hanayo , Irie Katsumasa , Segawa Katsumori , Hasegawa Kazuya , Fujiyoshi Yoshinori , Nagata Shigekazu , Abe Kazuhiro
Published: December 2019

ATP11C, a member of P4-ATPase flippase, exclusively translocates phosphatidylserine from the outer to the inner leaflets of the plasma membrane, and maintains the asymmetric distribution of phosphatidylserine in the living cell. However, the mechanisms by which ATP11C translocates phosphatidylserine remain elusive. Here we show the crystal structures of a human plasma membrane flippase, ATP11C-CDC50A complex, in an outward-open E2P conformation. Two phosphatidylserine molecules are in a conduit that continues from the cell surface to the occlusion site in the middle of the membrane. Mutations in either of the phosphotidylserine binding sites or along the pathway between significantly impairs specific ATPase and transport activities. We propose a model for phosphatidylserine translocation from the outer to the inner leaflet of the plasma membrane.
The transcriptome dynamics of single cells during the cell cycle
Authors: Schwabe Daniel , Formichetti Sara , Junker Jan Philipp , Falcke Martin , Rajewsky Nikolaus
Published: December 2019

Despite advances in single-cell data analysis, the dynamics and topology of the cell cycle in high-dimensional gene expression space remains largely unknown. Here, we use a linear analysis of transcriptome data to reveal that cells move along a circular trajectory in transcriptome space during the cell cycle. This movement occurs largely independently from other cellular processes. Non-cycling gene expression (changes in environment or epigenetic state) adds a third dimension and causes helical motion on a hollow cylinder. The circular trajectory shape indicates minimal acceleration of transcription, i.e. the cell cycle has evolved to minimize changes of transcriptional activity and its entailing regulatory effort. Thus, we uncover a general design principle of the cell cycle that may be of relevance to many other cellular differentiation processes.

One Sentence Summary

Cells traverse high-dimensional gene expression space in a 2D circular motion, thus minimizing changes of expression changes (“Acceleration”).
The mechanosensitive Piezo1 orchestrating angiogenesis is essential in bone fracture repair
Authors: Chen Peng , Zhang Gangyu , Jiang Shan , Ning Yile , Deng Bo , Pan Xianmei , Liu Silin , He Yu , Zhang Lei , Wan Rentao , Wu Zhiming , He Qi , Yin Jiang , Wang Haibin , Li Jing
Published: December 2019

Mechanical ion channel proteinPiezo1play vital roles in angiogenesis which has been proved to be high importance in varieties of biological processes. Bone formation in the fracture repair requires oxygen and nutrients from new blood vessels generated from fractured lesion. Understanding the underlying mechanisms linking angiogenesis and bone formation must be of great value for improved fracture healing. Here we employed mice with genetically modified endothelial specific depletion ofPiezo1channels to explore the hypothesis thatPiezo1is vital to the initiation of fracture healing. In this study, we demonstrated thatPiezo1expression and wide distribution along the bone and impaired endothelialPiezo1channels result in derangements in bone fracture repair. Intriguingly, the calcium activated proteolytic caplain activity severely disrupted during vascularization, precluded osteoblast maturation and mineralization and subsequently the phosphorylatedPI3K-AKTreduction. Furthermore,Piezo1endothelial disruption impairedNotchsignaling in bone union. These data collectively suggest thatPiezo1channels serve as a basis for clinical strategies to improve bone regeneration and treat delayed or nonunion in bone fracture.
Zebrafishdazlregulates cystogenesis upstream of the meiotic transition and germline stem cell specification and independent of meiotic checkpoints
Authors: Bertho Sylvain , Clapp Mara , Banisch Torsten U. , Bandemer Jan , Raz Erez , Marlow Florence L.
Published: December 2019

Fertility and gamete reserves are maintained by asymmetric divisions of the germline stem cells to produce new stem cells or daughters that differentiate as gametes. Before entering meiosis, differentiating germ cells (GCs) of sexual animals typically undergo cystogenesis. This evolutionary conserved process involves synchronous and incomplete mitotic divisions of a germ cell daughter (cystoblast) to generate sister cells connected by stable intercellular bridges that facilitate exchange of materials to support a large synchronous population of gamete progenitors. Here we investigate cystogenesis in zebrafish and identified Deleted in azoospermia (Dazl), a conserved vertebrate RNA binding protein as a regulator of this process. Analysis ofdazlmutants revealed an essential role for Dazl in regulating incomplete cytokinesis and germline cyst formation before the meiotic transition. Accordingly,dazlmutant GCs form defective ring canals, and ultimately remain as individual cells that fail to differentiate as meiocytes. In addition to promoting cystoblast divisions and meiotic entry,dazlfunction is required upstream of germline stem cell establishment and fertility.

Summary Statement

We show that zebrafishdazlis required for incomplete cytokinesis to generate germline cysts during cystogenesis, acts upstream of germline stem cell establishment, and is required for meiosis, and fertility.
KCNQ channels enable reliable presynaptic spiking and synaptic transmission at high-frequency
Authors: Zhang Yihui , Li Dainan , Darwish Youad , Trussell Laurence O. , Huang Hai
Published: December 2019

The presynaptic action potential (AP) results in calcium influx which triggers neurotransmitter release. For this reason, the AP waveform is crucial in determining the timing and strength of synaptic transmission. The calyx of Held nerve terminals of rat show minimum changes in AP waveform during high-frequency AP firing. We found that the stability of the calyceal AP waveform requires KCNQ K+channel activated during high-frequency spiking activity. High-frequency presynaptic spikes gradually led to accumulation of KCNQ channels in open states which kept interspike membrane potential sufficiently negative to maintain Na+channel availability. Accordingly, blocking KCNQ channels during stimulus trains led to inactivation of presynaptic Na+, and to a lesser extent KV1 channels, thereby reducing the AP height and broadening AP duration. Thus, while KCNQ channels are generally thought to prevent hyperactivity of neurons, we find that in axon terminals these channels function to facilitate high-frequency firing needed for sensory coding.

HIGHLIGHTS

KCNQ channels are activated during high-frequency firing

The activity of KCNQ channels helps the recovery of Na+and KV1 channels from inactivation and maintains action potential waveform

Reliable presynaptic action potential waveform preserves stable Ca2+influx and reliable synaptic signaling
ETHYLENE RESPONSE FACTOR 115integrates jasmonate and cytokinin signaling machineries to repress adventitious rooting inArabidopsis
Authors: Lakehal Abdellah , Dob Asma , Rahneshan Zahra , Novák Ondřej , Escamez Sacha , Alallaq Sanaria , Strnad Miroslav , Tuominen Hannele , Bellini Catherine
Published: December 2019

Jasmonate (JA), an oxylipin-derived phytohormone, plays crucial roles not only in plant immunity and defense against herbivorous insects but also in plant growth and developmental processes, including regeneration and organogenesis. However, the mechanistic basis of its mode of action and precise role in integrating other signaling cues are poorly understood. Here we provide genetic evidences that JA signaling acts in both NINJA-dependent and -independent modulation of the transcriptional activity of MYC transcription factors involved in the inhibition of adventitious root initiation (ARI). Our data show that NINJA-dependent JA signaling in pericycle cells blocks early events of ARI. Moreover, transcriptomic comparison ofninja-1myc2-322Bdouble mutant (which produce extremely few ARs) and wild type seedlings identified a novel molecular network governed by the APETALA2/ETHYLENE RESPONSE FACTOR 115 (ERF115) transcription factor. We demonstrate that JA-inducedERF115activates the cytokinin signaling machinery and thereby represses ARI. Altogether, our results reveal a molecular network involving cooperative crosstalk between JA and CK machineries that inhibits ARI.
Dreaming saints: exploratory authority and Islamic praxes of history in Central Java
Authors: Alatas Ismail Fajrie
Published: December 2019

This article examines dreaming as an Islamic practice of historical inquiry among traditionalist Muslims of Central Java, Indonesia. Combining insights from the anthropologies of Islam and history, it looks at alternative praxes of history, how they are interpreted through Islamic frameworks, and how they generate forms of religious authority. The article follows the work of a Sufi master, Habib Luthfi bin Yahya, in identifying old unmarked graves as saintly tombs through dreams. Successful history‐making projects have resulted in the increasing – albeit contested – recognition of Habib Luthfi's role as a dreaming saint, a form of Islamic authority premised on his perceived ability to oneirically explore the past on behalf of others and arbitrate history. By observing the connection between praxes of history and the formation of religious authority, the article calls for the broadening of anthropological studies of Islam beyond their current preoccupation with the religion's prescriptive dimension.
Uneasy translations: vernacularizing demography for post‐Soviet statecraft
Authors: Leykin Inna
Published: December 2019

The article explores a series of professional development seminars for state bureaucrats in the context of the moral panic over Russia's ‘demographic crisis’. It follows the vernacularization of social knowledge for state bureaucrats – a central practice that marks these pedagogical engagements. The article explores this practice's potentialities and limitations for effectively communicating social knowledge to administrative audiences. It grounds itself in the theoretical discussions of expertise and demonstrates how vernacularizing social knowledge for post‐Soviet statecraft shapes the social and political meanings of Russia's demographic crisis, investing state policies and discourses with authority.
Successful societies: Decision‐making and the quality of attentiveness
Authors: Stones Rob , Turner Bryan S.
Published: December 2019

Combining moral philosophy with sociological theory to build on themes introduced in Hall and Lamont’s Successful Societies (2009), the paper outlines a distinctive perspective. It holds that a necessary condition of successful societies is that decision‐makers base their decisions on a high level of attentiveness (concern and comprehension) towards subjectively valued and morally legitimate forms of life. Late modern societies consist of a plurality of forms of life, each providing grounds for what Alasdair MacIntyre has called internal goods—valued and morally valuable practices. The status of such goods is examined, and distinctions are drawn between their manifest and latent, and transposable and situationally specific, characteristics. We integrate this refined idea of internal goods into a developed conception of habitus that is both morally informed and situationally embedded. The sociological approach of strong structuration theory (SST) is employed to demonstrate how this conception of habitus can guide the critique of decision‐making that damages internal goods. We identify the most pervasive and invidious forms of damaging decision‐making in contemporary societies as those involving excessive forms of instrumental reasoning. We argue that our developed conception of habitus, anchored in the collectively valued practices of specific worlds, can be a powerful focus for resistance. Accounts of scholarship in higher education and of the white working class in America illustrate the specificities of singular, particular, social worlds and illuminate critical challenges raised by the perspective we advocate.
Implicit and explicit measures of teaching self‐efficacy and their relation to cultural heterogeneity: differences between preservice and in‐service teachers
Authors: Glock Sabine , Kleen Hannah
Published: December 2019

In this preliminary study, we explored preservice and in‐service teachers’ sense of teaching self‐efficacy with a well‐established questionnaire and a newly adapted implicit measure of the self‐concept Single‐Target Implicit Association Test. Teaching self‐efficacy is an important construct when it comes to the handling of culturally heterogeneous classes. Hence, teaching self‐efficacy might also contribute to teachers’ motivational orientations regarding and beliefs about ethnic minority students. Using a quasi‐experimental design, we presented preservice and in‐service teachers with both the implicit and explicit measures of teaching self‐efficacy and found no differences due to teacher expertise on the explicit measure. However, the implicit measure revealed that preservice teachers had much weaker cognitive associations between the construct of teaching self‐efficacy and their self‐concepts. Motivational orientations regarding and beliefs about ethnic minority students showed substantial correlations with the explicit measure of teaching efficacy, while the implicit measure correlated with the self‐efficacy regarding the teaching of ethnic minority students, but only for in‐service teachers. The findings highlight the importance of the consideration of implicit and explicit teaching efficacy for the teaching in culturally heterogeneous classes. These first results should inspire researchers to consider both kinds of measures in future research, particularly when investigating the relationship between teaching self‐efficacy and teachers’ beliefs about and motivational orientations regarding the inclusion of ethnic minority students.
Progress and challenges in engineering cyanobacteria as chassis for light‐driven biotechnology
Authors: Hitchcock Andrew , Hunter C. Neil , Canniffe Daniel P.
Published: December 2019

Cyanobacteria are prokaryotic phototrophs that, in addition to being excellent model organisms for studying photosynthesis, have tremendous potential for light‐driven synthetic biology and biotechnology. These versatile and resilient microorganisms harness the energy of sunlight to oxidise water, generating chemical energy (ATP) and reductant (NADPH) that can be used to drive sustainable synthesis of high‐value natural products in genetically modified strains. In this commentary article for the Synthetic Microbiology Caucus we discuss the great progress that has been made in engineering cyanobacterial hosts as microbial cell factories for solar‐powered biosynthesis. We focus on some of the main areas where the synthetic biology and metabolic engineering tools in cyanobacteria are not as advanced as those in more widely used heterotrophic chassis, and go on to highlight key improvements that we feel are required to unlock the full power of cyanobacteria for future green biotechnology.
The embryonic development of the bovine stomach revisited
Authors: Kalenberg Christina Alexandra , Stoffel Michael Hubert
Published: December 2019

The adult anatomy and physiology of the bovine (Bos taurus) stomach have been investigated extensively. Despite the many studies, however, the early development of the stomach has not yet been fully elucidated. The goal of the present study, therefore, was to review the available literature, to visualize the embryonic and early foetal development of the bovine stomach and to shed light on unresolved issues. The stomachs of fifteen bovine embryos and eleven foetuses from 26 to 80 days of gestation were photographed both in situ and after exenteration and critical point drying. A series of photographs was obtained that yielded a contiguous and comprehensive view of all the developmental changes that occurred until the virtually final configuration of the stomach was attained. In addition, the serosal surface was studied by electron microscopy, thus revealing subtle regional differences in the lining of the peritoneal cavity. Our observations corroborate the contention that all the compartments evolve from the fusiform primordium and that no outgrowth at the level of the oesophagus occurs. The greater curvature as well as the attachment line of the dorsal mesogastrium shift to the left, which is similar to the process in monogastrians. The rumen and reticulum develop from separate protrusions, and further compartmentalization results from constrictions and bulges and not from folding. Between 55 and 60 days of gestation, the entire bovine stomach except for the abomasum eventually relocates to its final position. In summary, previously debated key issues were addressed and integrated with current findings.
Long‐term trends of Chlamydia trachomatis in a clinic population at the Royal Women's Hospital, Melbourne
Authors: Garland Suzanne Marie , Subasinghe Asvini Kokila , Ahmed Navera , Jayasinghe Yasmin , Marceglia Alex
Published: December 2019

Background

Chlamydia trachomatis (C. trachomatis) prevalence has been reported to be increasing. Whether this is a true increase over time or confounded by increases in testing and/or use of more sensitive assays is to be determined.

Materials and Methods

One laboratory service has been detecting C. trachomatis for the past 30 years within the Royal Women's Hospital Melbourne. We conducted a retrospective audit of records over the period 1986–2016 from a clinic population routinely offered chlamydia screening. These were women presenting for family planning advice (termination of pregnancy, intrauterine device insertion or considered at high risk), who underwent chlamydia testing in the context of various diagnostic assays used over this time period. Assays utilised included culture, enzyme immunoassay (EIA), DNA probe, and nucleic acid amplification testing (NAAT). Non‐parametric test for trend was used to determine significant differences between prevalence estimates across ordered groups. Least squares regression was conducted to describe a linear trend matching known data points.

Results

Overall, there was no significant change for chlamydia prevalence which was 2.2%, in the 30‐year study period (P = 0.7). Over time diagnostic assays changed from culture, to EIA, DNA probe, to the more sensitive NAAT. The bulk of the positives were in women under 25 years of age (57%).

Conclusion

Chlamydia prevalence has been stable over 30 years, remaining a problem in young women. Screening for those at risk needs underscoring in a national sexual health program.
Editorial: effects of vedolizumab during pregnancy in the CONCEIVE study
Authors: Winter Rachel W.
Published: December 2019

LINKED CONTENT

This article is linked to Moens et al paper. To view this article, visit https://doi.org/10.1111/apt.15539.
Letter: is tenofovir superior to entecavir for hepatocellular carcinoma prevention in chronic hepatitis B? Authors’ reply
Authors: Yip Terry C.‐F. , Wong Grace L.‐H.
Published: December 2019

LINKED CONTENT

This article is linked to Brancaccio et al and Yuan et al papers. To view these articles, visit https://doi.org/10.1111/apt.15188 and https://doi.org/10.1111/apt.15603.
The effect of artificial insemination prior to transfer of a limited number of vitrified and warmed porcine embryos by open pulled straw (OPS) method on their survival ability for farrowing
Authors: Tajima Shigeyuki , Uchikura Kenzo , Kurita Takayuki , Kikuchi Kazuhiro
Published: December 2019

Embryo transfer (ET) of 20 porcine expanded blastocysts (ExBs) vitrified and warmed (VW) by open pulled straw (OPS) to a recipient allows stable piglet production. The efficiency of artificial insemination (AI) prior to ET of 10 VW ExBs for piglet production was investigated. For one trial, 10–15 VW ExBs from single donor were assigned, 10 were used for ET and the remains were assessed for their in vitro viability. In the non‐AI/ET group, 10 were transferred to each of five recipients. As AI/ET group, 10 were transferred to each of five recipients after AI. In AI/non‐ET group, only AI was performed to seven gilts. In the non‐AI/ET group, the pregnancy rate was 40%, but none of them farrowed. In the AI/ET group, all recipients produced piglets. Four (80.0%) delivered piglets from transferred VW ExBs. The survival rate of VW ExBs to term was 20.0% (10/50). In the AI/non‐ET group, six of the seven gilts farrowed. There was no difference in in vitro viability between the non‐AI/ET and AI/ ET groups (62.5% and 68.3%, respectively). AI prior to ET can be an appropriate way to maintain pregnancy and assist the development of a low number of VW ExBs to term.
The role of anti‐complement factor H antibodies in the development of atypical haemolytic uremic syndrome: a possible contribution to abnormality of platelet function
Authors: Fujisawa Madoka , Yasumoto Atsushi , Kato Hideki , Sugawara Yuka , Yoshida Yoko , Yatomi Yutaka , Nangaku Masaomi
Published: December 2019

Atypical haemolytic uremic syndrome (aHUS) is associated with complement system abnormality, such as production of complement factor H (CFH) autoantibodies. The growing evidence indicates complement overactivation on platelets is intimately involved in aHUS pathogenesis, besides endothelial injury. We here showed plasma from patients with anti‐CFH antibodies induced aggregation of washed platelets, while purified anti‐CFH antibodies suppressed aggregation. This suggested anti‐CFH antibody itself suppressed thrombosis, while other plasma factor including complement factors could overactivate the platelets, leading to aggregation, which augmented the notion the state of complement activation influenced by anti‐CFH antibodies is important in the aggregation of platelets in aHUS.
Group‐based meta‐emotion and emotion responses to intergroup threat
Authors: Pauketat Janet V. T. , Mackie Diane M. , Tausch Nicole
Published: December 2019

In a secularizing world, religious groups are increasingly threatened by anti‐religious groups. We present two studies investigating religious peoples’ responses to anti‐religious threats. We expected intergroup threats to shape group‐based emotions and behavioural intentions through a novel pathway whereby threat affects group‐based meta‐emotions: the ingroup’s perception of the outgroup’s emotions towards the ingroup. In Study 1, we experimentally manipulated threat and group salience with participants from two different cultures (British and Latinx/Hispanic). Study 1 demonstrated non‐interactive effects of threat increasing negative emotional responses and of group salience strengthening emotional responses. The results illustrated the role of group‐based meta‐emotions in predicting outgroup‐directed emotions and behavioural response intentions. Study 2 used a different manipulation of threat in an American sample and an identity‐based manipulation of salience to assess the impact of real‐world anti‐religious campaigns involving symbolic and realistic threats. Both threat types increased negative group‐based meta‐emotions, negative outgroup‐directed emotions, desire to respond, and opposition to the anti‐religious campaign compared to no threat. Overall, religious identity salience had little impact on outcomes. The indirect pathway through meta‐emotion replicated, suggesting the importance of considering this novel meta‐emotion pathway in intergroup relations.
Negative allosteric modulators of the human calcium‐sensing receptor bind to overlapping and distinct sites within the 7‐transmembrane domain
Authors: Josephs Tracy M. , Keller Andrew N. , Khajehali Elham , DeBono Aaron , Langmead Christopher J. , Conigrave Arthur D. , Capuano Ben , Kufareva Irina , Gregory Karen J. , Leach Katie
Published: December 2019

Background and Purpose

Negative allosteric modulators (NAMs) that target the calcium‐sensing receptor (CaS receptor) were originally developed for the treatment of osteoporosis by stimulating the release of endogenous parathyroid hormone, but failed in human clinical trials. Several chemically and structurally distinct NAM scaffolds have been described, but it is not known how these different scaffolds interact with the CaS receptor to inhibit receptor signalling in response to agonists.

Experimental Approach

In the present study, we used a mutagenesis approach combined with analytical pharmacology and computational modelling to probe the binding sites of four distinct NAM scaffolds.

Key Results

Although all four scaffolds bind to the 7‐transmembrane and/or extracellular or intracellular loops, they occupy distinct regions, as previously shown for positive allosteric modulators of the CaS receptor. Furthermore, different NAM scaffolds mediate negative allosteric modulation via distinct amino acid networks.

Conclusion and Implications

These findings aid our understanding of how different NAMs bind to and inhibit the CaS receptor. Elucidation of allosteric binding sites in the CaS receptor has implications for the discovery of novel allosteric modulators.