bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal Chondroplasty Technique for Costal Cartilage Harvesting and Contouring
Authors: Eravci Fakih Cihat , Ceylan Alper , Yilmaz Metin
Published: January 2020

Although costal cartilage autograft has versatile usage, harvesting the graft is an invasive procedure with potential risks for complications. Therefore, it is important to make every effort to minimize these risks. Moreover, sculpting costal cartilage to the desired shape is challenging and time-consuming because of the natural rigidity. This study aimed to evaluate cases of costal cartilage harvest in terms of the most important donor site complications and to present a novel, practical and inexpensive technique to overcome the challenges in costal cartilage harvesting and contouring. A retrospective review of patient records was made of 103 patients who underwent costal cartilage harvest by the senior author. Costal cartilage harvest was applied using either the thermal chondroplasty technique or the conventional technique on patients undergoing revision rhinoplasty surgery. The number of complications and operation times were compared between the 2 techniques.

A cohort of 47 patients (30 males, 17 females; mean age 34.5 years [range, 28–48 years]) underwent costal cartilage harvest using the thermal chondroplasty technique and a cohort of 56 patients (31 males, 25 females; mean age 36 years [range, 28–52 years]) underwent costal cartilage harvest with the conventional technique. The mean operation time for the costal cartilage harvest decreased by 7.5 minutes and the total operation time decreased by 17 minutes with the use of the thermal chondroplasty technique compared to the conventional technique (P < 0.05). Complications of 2 pneumothorax and 1 hematoma developed in the conventional technique group, and no complications were seen in the thermal chondroplasty group. The results of this study suggest that the thermal chondroplasty technique is safer and time-saving compared to the conventional technique.
The Influence of the Gonial Angle on the Initial Biomechanical Stability of the Plate Osteosynthesis in Polyurethane Mandibles With Angle Fractures
Authors: Sirin Yigit , Yildirimturk Senem , Ay Nida , Gencel Burc
Published: January 2020

The aim of the present study was to examine the biomechanical stability of the mandibular angle fractures (MAF) fixated with standard titanium miniplates in polyurethane models with different gonial angles (GA). Three custom molds were prepared for 3-dimensional printed mandibles with low, normal and high GA. Twenty polyurethane replicas were cast per group and standard MAFs were created on each sample. Fractures were stabilized with 1 4-hole standard titanium miniplate inserted over the superior alveolar border. Half of the samples were subjected to molar loading and the other half to the incisal loading up until 150 N force magnitude. The load-displacement curves and the horizontal moment arms were recorded and analyzed. The samples with high GA demonstrated greater displacement than those with normal and low GA during molar loading (P < 0.05 for both). After correcting for the effects of the moment arm, the incisal loading also resulted in higher mean displacement in the high GA group than the others (P < 0.05 for both) and the normal GA samples showed higher displacement after 100 N level compared to those in low GA (P < 0.05). Within the limits of this in vitro study, it can be concluded that the MAFs of the polyurethane mandibles with high GA fixated with 1 standard monocortical plate are more likely to demonstrate higher displacement values under the effects of the molar and incisal loadings than do the mandibles with normal and low GA.
Loss of Malar Bags in Lower Eyelid in Orbital Blow Out Fracture Reconstruction Following Pre- or Retro-Septal Transconjunctival Incision
Authors: Rahbin Samin , Liakos Alexander , Alinasab Babak
Published: January 2020

An isolated orbital blow out fracture may require surgical correction by accessing the infraorbital rim through a transconjunctival incision and inserting an orbital plate. The risk for aesthetic complications due to the incision has previously been well described. Sixty patients surgically treated using pre- or retro-septal transconjunctival incisions for isolated orbital blow out fractures were recruited and examined with regards to lower eyelid asymmetry. Forty-seven controls with conservative treatment were recruited and underwent a similar examination. A grading system for malar bags in the lower eyelids was set up to compare the 2 groups. All patients with moderate or severe malar bags on the nonoperated eyelid lost the malar bags on the operated side and developed asymmetry in the lower eyelids. No difference was found between the pre- and retro-septal approach. In this study we describe a new complication related to the transconjunctival incision and highlight the importance of informing patients in need of reconstruction of the orbital walls about the risk of postoperative asymmetry in the lower eyelids.
Reconstruction of Small and Medium-Sized Nasal Defects Using an Omega Advancement Flap
Authors: Altun Serdar , Bal Ali , Arpaci Enver
Published: January 2020

Introduction:

The nose is the most common area where malignant skin tumors occur. Repair with a flap after tumor excision provides esthetically and functionally acceptable results. In this study, we aimed to present the use of an omega (Ω) advancement flap, which can be applied in all anatomic regions of the nose, in 2 cm or smaller defects.

Methods:

Between 2015 and 2017, 18 patients underwent repair with omega (Ω) advancement flap in the nose after tumor removal. The pathology of 17 patients was basal cell carcinoma, and keratoacanthoma in 1 patient. The average defect diameter was 1.6 × 1.56 cm. The defects were in the nasal tip, nasal wing, lateral nasal wall, and supratip region. After tumors were excised from the safe margin, and were repaired using an omega advancement flap in the same session.

Results:

No flap necrosis, dehiscence, or infection was observed in the early postoperative period. Three patients developed hematoma under the flap, which was drained. No tumor recurrence was observed during the postoperative follow-up period. The results were satisfactory in all patients.

Conclusion:

The omega advancement flap is a safe procedure that can be easily applied in the same session for the repair of small-to-medium-sized nasal defects.
Clinical and Radiological Evaluation of Sinus Membrane Osteogenicity Subsequent to Internal Sinus Lifting and Implant Placement
Authors: Qabbani Ali Al , Bayatti Saad Wahby Al , Hasan Hayder , Samsudin AB , Kawas Sausan Al
Published: January 2020

To evaluate the ability of the maxillary sinus membrane to produce bone after internal sinus lifting and implant placement without adding exogenous bone graft, and to assess the quality of bone that has been produced 6 months postoperatively.

In this retrospective study, 10 subjects who underwent maxillary sinus floor lifting and met the inclusion criteria were selected and then subdivided into: Group-A underwent internal sinus elevation and placement of implants without the use of bone graft and Group-B underwent classical internal sinus lifting and placement of bovine bone particles and then placement of the implant as a control group. Radiofrequency analysis (RFA) values for measuring the Implant Stability Quotient (ISQ) of all implants were measured by Osstell device. CBCT was performed involving linear measurements of the site of sinus lifting for both groups.

High RFA values demonstrating excellent biomechanical stability were observed in Group-A compared to Group-B at 6 months postoperatively. Group-A showed a median of ISQ value;78 (8), 77(12), 79(3.5) and 77(4.50). Group-A was significantly higher in ISQ values than Group-B, which showed median and interquartile range (IQR) of ISQ value of [51(12.50), 54(14.50), 55(9), and 55(7.50)]. However, the amount of bone available in group B was significantly higher than group A; [3.5 mm (0.75) and 3.8 mm (0.69)].

Internal sinus lifting without bone graft has the ability of bone formation by osteogenic potential of the sinus membrane. Nevertheless, the high quality of bone being produced is of high importance for the success of an implant without the need for an exogenous bone graft. The newly formed bone was significantly of a better quality in Group-A. Thus, it is recommended to perform internal sinus lifting, without adding bone graft material and allow the osteogenic potential of the maxillary sinus membrane to produce its own osteogenic cells.
In Vitro Evaluation of a Novel Osteo-Inductive Scaffold for Osteogenic Differentiation of Bone-Marrow Mesenchymal Stem Cells
Authors: Chen Shuo , Yi Bao , Su Liang-bo , Zhang Yue-Rong , Chen Chang-Li
Published: January 2020

Background:

Demineralized bone matrices (DBMs) were demonstrated to be a promising candidate for bone regeneration by previous studies. However, the limited osteoinductivity of DBMs was insufficient for a better repairing of bone defect. Osteoblasts (OBs), the major cellular component of bone tissues, play an important role in the formation of new bone. The extracellular matrix (ECM) of OB is one of the main components of bone formation niche.

Objective:

To combine the DBMs with the ECM of OBs to construct a novel scaffold that could be used for bone reconstruction.

Methods:

In this study, OBs were cultured on the surface of DBMs for 10 days and removed by Triton X-100 and ammonium hydroxide to prepare the OBs-ECM-DBMs (OEDBMs). A series of material features such as residues of OBs and ECM, cytotoxity, and osteoinductive capability of OEDBMs were evaluated.

Results:

Low cell residues and low content of DNA were observed in OEDBMs. Compared with DBMs, OEDBMs possessed more bone tissues organic matrix proteins, such as osteocalcin, osteopontin, and collagen I. Rat bone marrow mesenchymal stem cells (rBMSCs) presented a good viability when cultured on both 2 materials. The significant upregulations of osteogenic genes and proteins of rBMSCs were observed in OEDBMs group compared with DBMs group.

Conclusion:

Taken together, these findings suggested that the OB-secreted ECM may be qualified as an ideal modification method for enhancing the performance of engineered bone scaffold.
Dynamical Changes of Mandible and Upper Airway After Mandibular Distraction Osteogenesis in Pierre Robin Sequence
Authors: Li Juan , Liu Yan , Yuan Xingang , Ding Xionghui , Guo Yongqiang , Qiu Lin
Published: January 2020

Objective:

To present the dynamical evaluation of mandible and upper airway size among Chinese infant patients following mandibular distraction osteogenesis in a short-term follow-up and compare predistraction measurements with a normal age- and sex-matched control.

Methods:

All the patients have undergone the computed tomography (CT) scan before mandibular distraction osteogenesis (T0), at the end of the distraction phase (T1), and 3 months after the end of the distraction phase before the distractor removal (T2). A CT analyzing computer software MIMICS was utilized to analyze the anatomic variables of upper airway size and mandible size. All analysis was based on a significance level of 0.05.

Results:

Eight patients with Pierre Robin sequence differed mainly in the mandibular body length and the minimum anteroposterior dimension of the retroglossal airway from the control. After mandibular distraction osteogenesis, the mandibular body length and the ramus height both increased significantly, the ramus height also increased after 3 months of consolidation. Only small increase in the airway dimension of the retroglossal area at T2 was observed compared with T1.

Conclusion:

Mandibular distraction osteogenesis is an effective modality in treating Pierre Robin sequence. Compared with normal control, the main difference may be the length of mandibular body and the area of the retroglossal airway. There may not be an increase in the diameter of airway and the length of mandibular body after 3 months of growth and development in Pierre Robin sequence. Individual surgical plan should be made to gain a better prognosis.
Alveolar Rhabdomyosarcoma Following Mandibular Distraction Osteogenesis
Authors: Hassan Bashar , Jacob DeAsia Dominique , Sisti Andrea , Zahler Stacey , Rampazzo Antonio , Bassiri Gharb Bahar
Published: January 2020

The authors present a rare case of anaplastic alveolar rhabdomyosarcoma (ARMS) occurring after Mandibular Distraction Osteogenesis. A 16-month-old male presented with a rapidly enlarging left lower jaw mass after removal of mandibular distractors placed shortly after birth for Pierre Robin Sequence and severe obstructive sleep apnea. Incisional biopsy of the mass revealed ARMS with anaplastic features. Although ARMS is an extremely rare entity, craniofacial surgeons should have a low threshold for seeking further diagnostic modalities of a growing mass postmandibular distraction.
Postoperative Chemotherapy Benefits Patients Who Received Preoperative Therapy and Pancreatectomy for Pancreatic Adenocarcinoma
Authors: Perri Giampaolo , Prakash Laura , Qiao Wei , Varadhachary Gauri R. , Wolff Robert , Fogelman David , Overman Michael , Pant Shubham , Javle Milind , Koay Eugene J. , Herman Joseph , Kim Michael , Ikoma Naruhiko , Tzeng Ching-Wei , Lee Jeffrey E. , Katz Matthew H. G.
Published: January 2020

Objective:

We sought to determine whether postoperative chemotherapy after preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) prolongs survival.

Background:

Data to support administering postoperative chemotherapy to patients who received preoperative therapy are lacking.

Methods:

All patients with PDAC who underwent pancreatectomy after preoperative therapy between 2010 and July 2017 at The University of Texas MD Anderson Cancer Center were identified. To control for selection bias, patients who received postoperative therapy and patients who did not were matched by propensity scores based on factors associated with the use of postoperative chemotherapy.

Results:

Among 245 patients treated with a median of 4 cycles of preoperative treatment and pancreatectomy, 155 (63%) initiated postoperative chemotherapy and 90 (37%) did not. Patients who received postoperative therapy had a higher median cancer antigen 19-9 level before surgery, larger median tumor diameter, higher rate of extrapancreatic invasion, and lower rate of pathologic major response. The propensity-matched cohort comprised 122 patients: 61 who received postoperative chemotherapy and 61 who did not. The median overall survival (OS) and recurrence free survival (RFS) for patients who received postoperative therapy were 42 and 17 months, respectively, versus 32 and 12 months for patients who did not (OS: P = 0.06; RFS: P = 0.04). Postoperative therapy was marginally associated with a longer OS (hazard ratio 0.55, 95% confidence interval 0.29–1.01; P = 0.05) and significantly associated with a longer RFS (hazard ratio 0.55, 95% confidence interval 0.29–0.96; P = 0.04).

Conclusions:

Despite being administered more frequently to patients with poor prognostic factors, postoperative chemotherapy after preoperative therapy and pancreatectomy for PDAC was of clinical benefit.
Impact of subchronic variable stress on ovariectomy and dendritic spine density in prefrontal cortex in mice
Authors: Iqbal Javed , Ma Xin-Ming
Published: January 2020

Major depressive disorder affects both women and men but females are two times more susceptible to the incidence of depression. The majority of stress models used male rodents, whereas fewer studies included females. Volumetric reductions have been reported in brain areas critical for the stress response, such as prefrontal cortex, and remodeling of dendritic spines has been proposed as an underlying factor. The aim of this study was to determine the effects of subchronic variable stress (SCVS) in males, sham, and specifically in ovariectomized (OVX) female mice. Here, we used 6 days SCVS model to induce depressive-like behavior, and only the OVX female mice showed the depressive-like behavior, while males showed resilient type behavior. Only OVX female mice showed significant increase in dendritic spine density in SCVS paradigm. Overall, this study suggests that (1) the effects SCVS produced on the behavior of males and OVX females and (2) SCVS may induce rapid and sustained changes of PL neurons, which highlights the importance of gonadal hormones in studying depression.
Brain source imaging based on movement-related cortical potentials induced by fatigue during self-paced handgrip contractions
Authors: Guo Feng , Zhang Tianyu , Hanson Nicholas J. , Zhang Rihui
Published: January 2020

Purpose

By using standard low resolution electromagnetic tomography (sLORETA), we sought to explore the changes in brain source localization when performing right handgrip contractions in the condition of muscular fatigue.

Methods

Ten healthy adults volunteered for this study, and were asked to perform repeated and intermittent self-paced right handgrip contractions at 30% maximal voluntary contraction based on visual feedback leading to fatigue of right flexor digitorum profundus. Motor potentials from the movement-related cortical potentials were extracted from the electroencephalogram and were further analyzed by sLORETA.

Results

The activated cortical regions were mainly the Brodmann area 6 on the superior frontal and medial frontal gyri, and the BA 10 on the frontal and medial frontal gyri. With the development of muscular fatigue, current density of the motor potential significantly increased and the activated cortical areas markedly enlarged.

Conclusion

In an attempt to maintain a target level of force during upper limb muscle fatigue induced by low intensity repetitive activation, the brain enhances the activation of sensorimotor cortex and enlarges the sensorimotor cortex area, especially in the ipsilateral hemisphere.
In-vitro neuroprotective effect and mechanism of 2β-hydroxy-δ-cadinol against amyloid β-induced neuronal apoptosis
Authors: Ji Zhi-Hong , Zhao Hong , Liu Chao , Yu Xin-Yu
Published: January 2020

Amyloid beta (Aβ) neurotoxicity plays a causative role in the pathogenesis of Alzheimer’s disease. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. In our previous study, a sesquiterpenoid compound 2β-hydroxy-δ-cadinol (HOC) which exhibited antiglutamate excitotoxicity effect was isolated from the fruits of Alpinia oxyphylla Miquel. Based on the antiglutamate excitotoxicity effect of HOC, in this study, we investigated the potential benefit of HOC in preventing Aβ(1–42)-induced neuronal apoptosis in cultured rat hippocampal neurons. The neuroprotective effect of HOC against Aβ(1–42)-induced neuronal apoptosis was assessed by Hoechst 33258 staining, reactive oxygen species (ROS) production, caspase-3 activation and caspase-3 activity. Results demonstrated that HOC treatment significantly prevented Aβ(1–42)-induced neuronal apoptosis. The underlying molecular mechanisms of HOC in preventing Aβ(1–42)-induced neuronal apoptosis may be via inhibiting Aβ(1–42)-induced ROS production, attenuating Aβ(1–42)-induced caspase-3 activation and inhibiting caspase-3 activity. This study suggests that HOC may be a potential agent for the prevention of Aβ neurotoxicity.
Somatostatin receptor 5-mediated modulation of outward K+ currents in rat retinal ganglion cells
Authors: Wu Na , Yin Ning , Zhang Yi , Li Qian , Sun Xing-Huai , Wang Zhongfeng
Published: January 2020

Somatostatin participants in multiple physiological functions by activating the five distinct G-protein-coupled receptors (sst1-sst5). In this study, we investigated the effect of sst5 activation on outward K+ currents in acutely isolated rat retinal ganglion cells using whole-cell patch-clamp techniques. Extracellular application of L-817,818, a specific sst5 agonist, significantly reduced outward K+ currents which was mainly the 4-aminopyridine and glybenclamide sensitive current components, but not the tetraethylammonium-sensitive one. The L-817,818 effect was mediated by sst5 since the suppression was eliminated when intracellular dialysis of the G-protein inhibitor GDP-β-S or extracellular application of the sst5 antagonist BIM-23056. Intracellular phospholipase C/protein kinase C signaling pathway was involved in the L-817,818 effect because the L-817,818 effect on K+ currents was inhibited when rat retinal ganglion cells were pretreated with U73122 or chelerythrine chloride. However, L-817,818 persisted to reduce the K+ currents when cAMP/protein kinase A, calcium/calmodulin-dependent protein kinase II and mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathways were blocked respectively. These results suggest that sst5 activation suppresses 4-aminopyridine and glybenclamide-sensitive K+ currents in rat retinal ganglion cells by stimulating intracellular phospholipase C/protein kinase C signaling pathway, thereby regulating the rat retinal ganglion cell excitability.
A translational kidney organoid system bolsters human relevance of clinical development candidate
Authors: Westerling-Bui Amy , Soare Thomas W. , Venkatachalan Srinivasan , DeRan Michael , Fast Eva Maria , Fanelli Alyssa B. , Kyrychenko Sergii , Hoang Hien , Corriea Grinal M. , Zhang Wei , Yu Maolin , Daniels Matthew , Malojcic Goran , Pan-Zhou Xin-Ru , Ledeboer Mark W. , Harmange Jean-Christophe , Emani Maheswarareddy , Tibbitts Thomas T. , Reilly John F. , Mundel Peter
Published: January 2020

A major challenge in drug discovery is gaining confidence in the human relevance of pre-clinical animal studies. While human iPSC-derived organoids offer exciting opportunities to address this, concerns about applicability and scalability remain. Here, we report a high-throughput organoid platform for assessment of kidney disease targeting compounds in a human system. We confirmed platform reproducibility by single cell RNA-Seq (scRNA-Seq) and derived a NanoString panel for efficient quality control (QC). Organoid transplantation in rats for 2 to 4 weeks promoted organoid maturation and vascularization. In functional studies, cyclosporine A (CsA) and GFB-887, a novel TRPC5 channel blocker, protected kidney organoids from injury. Pharmacodynamic studies with GFB-887 delivered orally to rats were also successfully performed in human transplanted organoids. These data show how human organoids can deliver confidence in taking development candidate compounds to the clinic, fulfilling their promise to revolutionize drug discovery.
MONN: a Multi-Objective Neural Network for Predicting Pairwise Non-Covalent Interactions and Binding Affinities between Compounds and Proteins
Authors: Li Shuya , Wan Fangping , Shu Hantao , Jiang Tao , Zhao Dan , Zeng Jianyang
Published: January 2020

Computational approaches for inferring the mechanisms of compound-protein interactions (CPIs) can greatly facilitate drug development. Recently, although a number of deep learning based methods have been proposed to predict binding affinities and attempt to capture local interaction sites in compounds and proteins through neural attentions, they still lack a systematic evaluation on the interpretability of the identified local features. In addition, in these previous approaches, the exact matchings between interaction sites from compounds and proteins, which are generally important for understanding drug mechanisms of action, still remain unknown. Here, we compiled the first benchmark dataset containing the inter-molecular non-covalent interactions for more than 10,000 compound-protein pairs, and used it to systematically evaluate the interpretability of neural attentions in existing prediction models. We developed a multi-objective neural network, called MONN, to predict both non-covalent interactions and binding affinity for a given compound-protein pair. MONN uses convolution neural networks on molecular graphs of compounds and primary sequences of proteins to effectively capture the intrinsic features from both inputs, and also takes advantage of the predicted non-covalent interactions to further boost the accuracy of binding affinity prediction. Comprehensive evaluation demonstrated that while the previous neural attention based approaches fail to exhibit satisfactory interpretability results without extra supervision, MONN can successfully predict non-covalent interactions on our benchmark dataset as well as another independent dataset derived from the Protein Data Bank (PDB). Moreover, MONN can outperform other state-of-the-art methods in predicting compound-protein binding affinities. In addition, the pairwise interactions predicted by MONN displayed compatible and accordant patterns in chemical properties, which provided another evidence to support the strong predictive power of MONN. These results suggested that MONN can offer a powerful tool in predicting binding affinities of compound-protein pairs and also provide useful insights into understanding the molecular mechanisms of compound-protein interactions, which thus can greatly advance the drug discovery process. The source code of the MONN model and the dataset creation process can be downloaded fromhttps://github.com/lishuya17/MONN.
Single cell epigenomic atlas of the developing human brain and organoids
Authors: Ziffra Ryan S. , Kim Chang N. , Wilfert Amy , Turner Tychele N. , Haeussler Maximilian , Casella Alex M. , Przytycki Pawel F. , Kreimer Anat , Pollard Katherine S. , Ament Seth A. , Eichler Evan E. , Ahituv Nadav , Nowakowski Tomasz J.
Published: January 2020

Dynamic changes in chromatin accessibility coincide with important aspects of neuronal differentiation, such as fate specification and arealization and confer cell type-specific associations to neurodevelopmental disorders. However, studies of the epigenomic landscape of the developing human brain have yet to be performed at single-cell resolution. Here, we profiled chromatin accessibility of >75,000 cells from eight distinct areas of developing human forebrain using single cell ATAC-seq (scATACseq). We identified thousands of loci that undergo extensive cell type-specific changes in accessibility during corticogenesis. Chromatin state profiling also reveals novel distinctions between neural progenitor cells from different cortical areas not seen in transcriptomic profiles and suggests a role for retinoic acid signaling in cortical arealization. Comparison of the cell type-specific chromatin landscape of cerebral organoids to primary developing cortex found that organoids establish broad cell type-specific enhancer accessibility patterns similar to the developing cortex, but lack many putative regulatory elements identified in homologous primary cell types. Together, our results reveal the important contribution of chromatin state to the emerging patterns of cell type diversity and cell fate specification and provide a blueprint for evaluating the fidelity and robustness of cerebral organoids as a model for cortical development.
Regulation of Prefrontal Patterning, Connectivity and Synaptogenesis by Retinoic Acid
Authors: Shibata Mikihito , Pattabiraman Kartik , Lorente-Galdos Belen , Andrijevic David , Xing Xiaojun , Sousa Andre M. M. , Santpere Gabriel , Sestan Nenad
Published: January 2020

The prefrontal cortex (PFC) and its reciprocal connections with the mediodorsal thalamus (MD) are crucial for cognitive flexibility and working memory1–4and are thought to be altered in several disorders such as autism spectrum disorder5, 6and schizophrenia6–9. While developmental mechanisms governing regional patterning of the rodent cerebral cortex have been characterized10–15, the mechanisms underlying the development of PFC-MD connectivity and the lateral expansion of PFC with distinct granular layer 4 in anthropoid primates16–23have not been elucidated. Here we report increased concentration of retinoic acid (RA), a signaling molecule involved in brain development and function24, 25in the prospective PFC areas of human and macaque, compared to mouse, during mid-fetal development, a crucial period for cortical circuit assembly. In addition, we observed the lateral expansion of RA synthesizing enzyme, ALDH1A3, expression in mid-fetal macaque and human frontal cortex, compared to mouse. Furthermore, we found that enrichment of RA signaling is restricted to the prospective PFC byCYP26B1, a gene encoding an RA-catabolizing enzyme upregulated in the mid-fetal motor cortex. Gene deletion in mice revealed that RA signaling through anteriorly upregulated RA receptors,RxrgandRarb, andCyp26b1-dependent catabolism is required for the proper molecular patterning of PFC and motor areas, the expression of the layer 4 markerRORB, intra-PFC synaptogenesis, and the development of reciprocal PFC-MD connectivity. Together, these findings reveal a critical role for RA signaling in PFC development and, potentially, its evolutionary expansion.
Hominini-Specific Regulation ofCBLN2Increases Prefrontal Synaptogenesis
Authors: Shibata Mikihito , Pattabiraman Kartik , Muchnik Sydney K. , Sestan Nenad
Published: January 2020

The similarities and differences between nervous systems of various species result from developmental constraints and specific adaptations1-4. Comparative analyses of the prefrontal cortex (PFC), a region of the cerebral cortex involved in higher-order cognition and complex social behaviors, have identified confirmed and putative human-specific structural and molecular changes4-8. For example, one crucial specialization involves the anterior-posterior gradient in synaptic density, with a disproportionately higher number of dendritic spines specifically in the human PFC compared to other analyzed primates5. These changes are likely mediated by divergence in spatio-temporal patterns of gene expression9-17, which are prominent in the mid-fetal human cerebral neocortex15,18-20. Analyzing developmental human and macaque brain transcriptomic data15,20, we identified a transient PFC- and laminar-specific upregulation of the gene encoding cerebellin 2 (CBLN2), a neurexin (NRXN) and glutamate receptor delta (GRID/GluD)-associated synaptic organizer21-27, in human mid-fetal development coinciding with the initiation of synaptogenesis. Moreover, we show that this difference in expression level and laminar distribution ofCBLN2, is due to Hominini-specific deletions affecting SOX5 binding sites within a retinoic acid-responsiveCBLN2enhancer.In situgenetic humanization of the mouseCbln2enhancer drives increased and ectopic laminarCbln2expression and promotes glutamatergic and GABAergic synaptogenesis specifically in the PFC. These findings identify a putative genetic and molecular basis for the disproportionately increased connectivity in the Hominini PFC and suggest a developmental mechanism linking dysfunction of the NRXN-GRID-CBLN2 complex, to the pathogenesis of neuropsychiatric disorders.
Acetylation is required for NLRP3 self-aggregation and full activation of the inflammasome
Authors: Zhao Kai , Zhang Yening , Xu Xueming , Liu Liping , Huang Lingmin , Luo Ruiheng , Li Jing , Zhang Ningjie , Lu Ben
Published: January 2020

The full activation of NLRP3 inflammasome needs two sequential signals: the fist priming signal and the second assembly signal. Various stimuli including infections and stress signals can provide the assembly signal. However, how NLRP3 detects diverse stimuli and becomes fully activated remain largely unknown. In this study, we found the second signal specially triggers the acetylation of NLRP3, which facilitates the aggregation of NLRP3 and its interaction with ASC and NEK7, thus promoting the assembly of inflammasome. Meanwhile, by employing pharmacological and molecular approaches, we identified KAT5 as a regulator of NLRP3 acetylation and activation. Furthermore, KAT5 specific inhibitor-NU9056 exhibited a robust suppressive effect on NLRP3 inflammasome bothin vitroandin vivo. Thus, our study reveals a new mechanism for NLRP3 full activation and suggests targeting NLRP3 acetylation may provide a new approach for treatment of NLRP3 associated diseases.
Determinants of growth and body size inAustrolebiasSouth-American annual killifish
Authors: Helmstetter Andrew , Van Dooren Tom JM
Published: January 2020

Patterns of size variation in fish are supposed to be generated by growth differences, not by egg or hatchling size variation. However, annual killifish live in temporary ponds with a limited time period available for growth and reproduction. It has therefore been hypothesized that among annual killifish, hatchling size variation should be of large relative importance to generate adaptive adult size variation. Using growth curves of 203 individuals from 18Austrolebiasspecies raised in a common environment, we demonstrate that hatchling size variation indeed is a main determinant of adult size variation in annual killifish, in agreement with the time constraint hypothesis. Furthermore, we find an increased early growth rate in piscivorous species augmenting their difference in size from small congeneric species. This should be adaptive if size differences determine predation success. Environmental effects of spatial location of the population of origin on hatchling size and growth suggest that the time constraint might be weakened in populations occurring near the Atlantic coast. Our study reveals how extreme environments demand specific life history solutions to achieve adaptive size variation and that there might be scope for local adaptations in growth trajectories.
Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm
Authors: Castiglione Melissa , Mazzeo Christopher , Jiang Ya-Ping , Chen Juei-Suei , Kaushansky Kenneth , Yin Wei , Lin Richard Z. , Zheng Haoyi , Zhan Huichun
Published: January 2020

Rational

The myeloproliferative neoplasms (MPNs) are clonal hematological malignancies characterized by hematopoietic stem cell expansion and overproduction of mature blood cells. Cardiovascular complications are the leading cause of morbidity and mortality in patients with MPNs. The acquired kinase mutation JAK2V617F plays a central role in these disorders. Mechanisms responsible for cardiovascular dysfunction in MPNs are not fully understood, limiting the effectiveness of current treatment.

Objective

Vascular endothelial cells (ECs) play critical roles in the regulation of hemostasis and thrombosis. ECs carrying the JAK2V617F mutation can be detected in patients with MPNs. The goal of this study was to test the hypothesis that the JAK2V617F mutation alters endothelial function to promote cardiovascular complications in patients with MPNs.

Methods and Results

We employed murine models of MPN in which the JAK2V617F mutation is expressed in specific cell lineages. When JAK2V617F is expressed in both blood cells and vascular ECs, the mice developed MPN and spontaneous, age-related dilated cardiomyopathy with an increased risk of sudden death as well as a prothrombotic and vasculopathy phenotype on histology evaluation. We showed that JAK2V617F-mutant ECs are required for this cardiovascular disease phenotype and the mutation can alter endothelial cell function. Finally, in a more therapeutically oriented approach, we demonstrated that transplantation with wild-type donor marrow cells can improve cardiac function by reversing the left ventricle remodeling process in this JAK2V617F-positive MPN murine model.

Conclusions

These findings suggest that the JAK2V617F mutation alters vascular endothelial function to promote cardiovascular complications in MPNs. Therefore, targeting the MPN vasculature represents a promising new therapeutic strategy for patients with MPNs.
Increased urocortin 3 levels are associated with the risk of having type 2 diabetes mellitus
Authors: Alarslan Pınar , Unal Kocabas Gokcen , Demir Ismail , Guler Aslı , Bozkaya Giray , Aslanipour Behnaz , Calan Mehmet
Published: January 2020

Background

Urocortin 3 (UCN3) is a peptide hormone playing a pivotal role in glucose and lipid metabolisms. However, its clinical implications remain unclear. Our aims were to investigate the altered levels of UCN3 in newly diagnosed type 2 diabetes mellitus (nT2DM) patients in comparison to subjects with normal glucose tolerance (NGT) and to determine the presence of any possible link between UCN3 levels and metabolic parameters.

Methods

Eighty nT2DM and 80 age‐, body mass index (BMI)‐, and gender‐matched NGT subjects were enrolled into this case‐control study. The circulating UCN3 levels were measured using the enzyme‐linked immunoabsorbent assay (ELISA). Metabolic parameters of enrolled subjects were also determined. A standard 75‐g 2‐hour oral glucose tolerance test was used for diagnosis of type 2 diabetes mellitus (T2DM).

Results

UCN3 levels were higher in subjects with nT2DM than in controls (115.64 ± 39.26 vs 86.16 ± 22.81 pg/mL, P < .001). UCN3 levels were increased in subjects with metabolic syndrome compared to subjects without metabolic syndrome in both nT2DM and NGT groups. UCN3 levels showed a positive correlation with BMI in both groups. Moreover, UCN3 levels were positively and independently associated with insulin, fasting blood glucose, insulin resistance, 2‐hour plasma glucose, glycosylated hemoglobin, and triglycerides, whereas UCN3 levels were negatively and independently associated with high‐density lipoprotein cholesterol. According to logistic regression analysis, increased risk of T2DM and metabolic syndrome were parallel with the highest elevated levels of UCN3.

Conclusions

Increased levels of UCN3 are associated with unfavorable metabolic profiles in T2DM, indicating a potential role of UCN3 in glucose and lipid metabolisms in T2DM.
Effects of regional economics on the online sale of protected parrots and turtles in China
Authors: Ye Yun‐Chun , Yu Wen‐Hua , Newman Chris , Buesching Christina D. , Xu Ya‐li , Xiao Xiao , Macdonald David W. , Zhou Zhao‐Min
Published: January 2020

The sale of wild animals, including protected species, may relate to regional differences in socio‐politics, culture, and economic development. A better understanding of how these factors affect the illegal wildlife trade is therefore necessary to optimize the deployment of conservation resources and policing. To evaluate these factors in relation to the trade‐in protected animals as pets, we surveyed China's popular consumer‐to‐consumer website, Taobao.com (analogous to eBay), and found that over 70,000 individual live parrots and turtles (totaling 46 and 49 protected species, respectively) were sold in just 150 days. Using analyses that attempted to account for species richness estimation and autocorrelation effects, we identified that regional economics promoted the occurrence and extent of pet sales. The provenance of these traded animals was ambiguous, but their vast numbers raise two concerns: if any proportion was sourced illegally from the wild, it is of conservation concern; whereas any bred illegally in captivity raise animal welfare concerns, because this would be unregulated. In the context of rapid economic development in China, it is thus important to reform the legislation that currently allows these commonly traded pet species to slip through the net intended to police animal welfare and illegal animal trading.
Laboratory Technician Assessment of the Quality of Single‐Unit Crown Preparations and Impressions as Predictors of the Clinical Acceptability of Crowns as Determined by the Treating Dentist: Findings from the National Dental Practice‐Based Research Network
Authors: McCracken Michael S. , Litaker Mark S. , Thomson Alexandra E. S. , Slootsky Alan , Gilbert Gregg H. ,   National Dental PBRN Collaborative Group
Published: January 2020

Purpose

In‐laboratory assessment by laboratory technicians may offer insight to increase clinical success of dental crowns, and research in this area is lacking.

Materials and Methods

Dentists in the National Dental Practice‐Based Research Network enrolled patients in a study about single‐unit crowns; laboratory technicians evaluated the quality of tooth preparations and impressions. The primary outcome for each crown was clinical acceptability (CAC), as judged by the treating dentist. A secondary outcome was “Goodness of Fit (GOF),” a composite score of several aspects of clinical fit, also judged by the study dentist. A mixed‐effects logistic regression was used to analyze associations between laboratory technician ratings and the CAC and GOF.

Results

Dentists (n = 205) evaluated 3731 crowns. Technicians ranked the marginal detail of impressions as good or excellent in 92% of cases; other aspects of the impression were ranked good or excellent 88% of the time. Regarding tooth preparation, about 90% of preparations were considered adequate (neither excessive nor inadequate reduction). Factors associated with higher CAC were more preparation taper, and use of optical imaging. Factors associated with better GOF were higher impression quality, greater occlusal reduction, more preparation taper, and optical imaging.

Conclusions

Overall quality of preparations and impressions was very high, as evaluated by laboratory technicians. Several clinical parameters were associated with higher CAC and GOF. Clinicians who struggle with crown remakes might consider less conservative tooth preparation, as well as using digital impression technology.
Effect of starter culture on staphylococcal enterotoxin and thermonuclease production in dry sausage
Authors: Niskanen A , Nurmi E
Published: January 2020

Different amounts of enterotoxin A-, B-, and C1-producing staphylococci were added to dry sausage prepared by normal processes, either alone or in conjunction with a starter culture (micrococci and lactobacilli). The sausage was examined after 0, 3, 7, 14, and 30 days for staphylococci, micrococci, and lactobacilli, and measurements were made of water activity, pH, enterotoxin, and thermostable nuclease. The results showed that in the absence of starter culture measurable amounts of enterotoxin A were formed in a 200-g sample of dry sausage in 3 days, the level of Staphylococcus aureus infection being over 10(6) cells/g. Enterotoxin B was not found, although the total number of staphylococci was over 10(8) cells/g. Enterotoxin C1 was observed when the Staphylococcus count was about 8 X 10(7) cells/g, but was no longer detectable after 7 days. The starter culture prevented the production of enterotoxin A in all cases investigated. By contrast, a very high-level inoculation of an enterotoxin C1-producing strain gave a positive result after 3 days of incubation even in the presence of a starter culture. Heat-stable nuclease was observed in all sausages to which enterotoxin-producing staphylococci were added. The cell count determined in a sample of sausage had no definite correlation with the thermonuclease activity of the sample.
Stimulatory effect of dihydroxyphenyl compounds on the aerotolerance of Spirillum volutans and Campylobacter fetus subspecies jejuni
Authors: Bowdre J H , Krieg N R , Hoffman P S , Smibert R M
Published: January 2020

The aerotolerance of the microaerophilic bacterium Spirillum volutans was greatly stimulated in a defined medium by the presence of dihydroxyphenyl ferric iron-binding compounds such as nor-epinephrine at 10(-5) to 10(-6) M. Dihydroxyphenyl compounds at 2 X 10(-4) M, or iron salts (ferrous or ferric) at high concentration, greatly increased the aerotolerance of a strain of Campylobacter fetus subsp. jejuni when grown on streak plates of Brucella agar. The results suggest that the microaerophilism of these organisms might in part be caused by a failure to synthesize microbial ferric iron-binding compounds at sufficient levels to support aerobic growth.
Inhibitory Effect of Light on Growth-Supporting Properties of Eosin Methylene Blue Agar
Authors: Girolami R. L. , Stamm J. M.
Published: January 2020

Exposure of eosin methylene blue agar to visible light can alter the ability of that medium to support microbial growth.
Proteus
species were most sensitive to the photodynamic action.
Rapid determination of dipicolinic acid in the spores of Clostridium species by gas-liquid chromatography
Authors: Tabor M W , MacGee J , Holland J W
Published: January 2020

A gas-liquid chromatographic procedure has been developed to quantitate dipicolinic acid in bacterial spores. The culture, washed from a plate, was hydrolyzed with acid containing the internal standard, pyridine-2,4-dicarboxylate, and then extracted into methyl isobutyl ketone. The internal standard and dipicolinic acid were then extracted into a small volume of trimethylphenylammonium hydroxide. Injection of the resultant quaternary ammonium salts into a gas chromatograph yielded, via thermal decomposition, the methyl ester derivatives of the dipicolinic acid and the internal standard. The amount of dipicolinic acid in the sample was determined from a standard curve. The method was sensitive to 100 ng of dipicolinic acid per sample and was 1,000 to 5,000 times more sensitive than the commonly used methods. Preparation of the sample required less than 1.5 h and less than 15 min of the analyst's time.
Biodegradation of phthalic acid esters in river water and activated sludge
Authors: Saeger V W , Tucker E S
Published: January 2020

The primary and ultimate biodegradability of phthalic acid, monobutyl phthalate, and five structurally diverse phthalic acid ester plasticizers in river water and activated sludge samples were determined via ultraviolet spectrophotometry, gas chromatography, and CO2 evolution. The compounds studied underwent rapid primary biodegradation in both unacclimated river water and acclimated activated sludge. When activated sludge acclimated to phthalic acid esters was used as the inoculum for the CO2 evolution procedure, greater than 85% of the total theoretical CO2 was evolved. These studies demonstrate that the phthalic acid ester plasticizers and intermediate degradation products readily undergo ultimate degradation in different mixed microbial systems at concentrations ranging from 1 to 83 mg/liter.
Macromolecular syntheses during biosynthesis of prodigiosin by Serratia marcescens
Authors: Williams R P , Scott R H , Lim D V , Qadri S M
Published: January 2020

Amino acids that were utilized as sole sources of carbon and nitrogen for growth of Serratia marcescens Nima resulted in biosynthesis of prodigiosin in non-proliferating bacteria. Addition of alanine, proline, or histidine to non-proliferating cells incubated at 27 C increased the rate of protein synthesis and also caused biosynthesis of prodigiosin. No increase in the rate of protein synthesis was observed upon the addition of amino acids that did not stimulate prodigiosin biosynthesis. Increased rates of synthesis of ribonucleic acid (RNA) and of deoxyribonucleic acid (DNA) (a small amount) also occurred after addition of amino acids that resulted in biosynthesis of prodigiosin. After incubation of 24 h, the total amount of protein in suspensions of bacteria to which alanine or proline was added increased 67 and 98%, respectively. Total amounts of DNA and of RNA also increased before synthesis of prodigiosin. The amounts of these macromolecules did not increase after addition of amino acids that did not induce biosynthesis of progidiosin. However, macromolecular synthesis was not related only to prodigiosin biosynthesis because the rates of DNA, RNA, and protein synthesis also increased in suspensions of bacteria incubated with proline at 39 C, at which temperature no prodigiosin was synthesized. The quantities of DNA, RNA, and protein synthesized were lower in non-proliferating cells than in growing cells. The data indicated that amino acids causing biosynthesis of prodigiosin in non-proliferating cells must be metabolized and serve as sources of carbon and of nitrogen for synthesis of macromolecules and intermediates. Prodigiosin was synthesized secondarily to these primary metabolic events.