Miracle-dz/UniFAR-FTUs huggingface dataset:
Trophectoderm-Specific Knockdown of LIN28 Decreases Expression of Genes Necessary for Cell Proliferation and Reduces Elongation of Sheep Conceptus

LIN28 inhibits let-7 miRNA maturation which prevents cell differentiation and promotes proliferation. We hypothesized that the LIN28-let-7 axis regulates proliferation-associated genes in sheep trophectoderm in vivo. Day 9-hatched sheep blastocysts were incubated with lentiviral particles to deliver shRNA targeting LIN28 specifically to trophectoderm cells. At day 16, conceptus elongation was significantly reduced in LIN28A and LIN28B knockdowns. Let-7 miRNAs were significantly increased and IGF2BP1-3, HMGA1, ARID3B, and c-MYC were decreased in trophectoderm from knockdown conceptuses. Ovine trophoblast (OTR) cells derived from day 16 trophectoderm are a useful tool for in vitro experiments. Surprisingly, LIN28 was significantly reduced and let-7 miRNAs increased after only a few passages of OTR cells, suggesting these passaged cells represent a more differentiated phenotype. To create an OTR cell line more similar to day 16 trophectoderm we overexpressed LIN28A and LIN28B, which significantly decreased let-7 miRNAs and increased IGF2BP1-3, HMGA1, ARID3B, and c-MYC compared to control. This is the first study showing the role of the LIN28-let-7 axis in trophoblast proliferation and conceptus elongation in vivo. These results suggest that reduced LIN28 during early placental development can lead to reduced trophoblast proliferation and sheep conceptus elongation at a critical period for successful establishment of pregnancy.
New Insights into the Pathogenesis of Intradialytic Hypertension

Intradialytic hypertension is identified as an independent predictor of adverse clinical outcome in hemodialysis patients. Little is known about its pathophysiological mechanism. The aim of this study is to provide new insights into the mechanisms underlying this arterial pressure dysregulation. 62 subjects on chronic hemodialysis were included in this study. Blood pressure was monitored before, during and following each dialysis session for a 3-month period. Pre- and post-dialysis blood samples were drawn from all the subjects to perform immunoassays, monocyte extractions and western blot analyses. Blood pressure values separated the subjects with in two groups: normal blood pressure (n=53) and intradialytic hypertension (n=9) groups. Renin, angiotensin converting enzyme I and aldosterone plasma concentrations significantly diverged between the groups. Vascular endothelial nitric oxide assessment revealed significantly lower plasma L-citrulline and angiotensin-converting enzyme II in post-dialysis intradialytic hypertensive patients, along with high endothelin I and asymmetric dimethylarginine concentrations. Plasma collectrin levels were significantly higher in pre and post-dialysis intradialytic hypertensive group compared to a normal blood pressure group. Post-dialysis interleukin 6 was significantly higher in intradialytic hypertensive group compared to normal blood pressure group. Finally, pre-dialysis intradialytic hypertension was associated with significantly higher circulating vascular endothelial growth factor C with monocytic up-regulation of vascular endothelial growth factor C/tonicity-responsive enhancer binding protein expression. Impairment of vascular endothelial nitric oxide key regulatory elements, as well as monocytic vascular endothelial growth factor C seems to be more prevalent in intradialytic hypertension. These clues could pinpoint novel therapeutic interventions in intradialytic hypertension management.
α7 nicotinic acetylcholine receptors at the glutamatergic synapse

Nicotinic acetylcholine receptor (nAChR) activation is neuroprotective and nicotine is a cognitive enhancer. Loss of nAChRs, deposition of tau neurofibrillary tangles, cleavage of amyloid precursor protein (APP) and inflammation are well documented in the pathogenesis of Alzheimer’s disease (AD). Sequential cleavage of APP by β- and γ-secretase enzymes generates soluble Aβ peptides, with oligomeric forms of Aβ implicated in both the control of synaptic excitability and dysregulation of synaptic transmission and induction of neuronal death in AD. Aβ production is inhibited by calcium-dependent recruitment of α-secretase, as exemplified by activation of N-methyl-D-aspartate receptors (NMDAR). All neurodegenerative diseases are associated with inflammation, arising from altered homeostasis of the innate immune system, resulting in heightened activation of immune cells and induction of a pro-inflammatory environment. Stimulation of the α7 subtype of nAChR is anti-inflammatory and also enhances cognition and promotes neuronal survival. This work addressed the hypotheses that stimulation of highly calcium-permeable α7nAChR inhibits Aβ production by promoting α-secretase-mediated processing of APP and also modulates inflammatory cellular behaviour of microglia. Thus, this study assessed the role of α7nAChR at glutamatergic synapses, through probing effects on APP processing and phagocytosis in primary cortical neurons and microglia, respectively. Primary cortical neurons expressed functional α7nAChR and glutamate receptors, and through a number of experimental approaches, including immunoblotting and a cleavage reporter assay, results indicated α7nAChR activation with the α7nAChR-selective agonist PNU-282987 and positive allosteric modulator PNU-120596 had no effect on APP and Tau, in contrast to NMDAR activation that significantly modulated these proteins. Data suggest low expression of α7nAChR, coupled with distinct localisation of presynaptic α7nAChR and postsynaptic APP could explain the lack of effect. In addition, primary microglia were highly responsive to lipopolysaccharide and possessed functional α7nAChR that coupled to ERK phosphorylation. Microglial α7nAChR activation promoted neuroprotective phagocytic behaviour, in agreement with the ‘cholinergic anti-inflammatory pathway’. This study supports the hypothesis that α7nAChR are modulators of anti-inflammatory behaviour, thus α7nAChR-selective ligands are viable candidates for the treatment of AD and promoting cognitive enhancement.
Systematics and Phylogeny of Holarctic Genera of Nepticulidae (Lepidoptera, Heteroneura: Monotrysia)

A revised classification of the Holarctic genera of Nepticulidae is provided. Eight genera belonging to the nominal subfamily are recognised and redefined. They are Enteucha Meyrick (= Johanssonia Borkowski, Artaversala Davis, Oligoneura Davis), Stigmella Schrank (including Astigmella Puplesis), Simplimorpha Scoble in the Nepticulini and Acalyptris Meyrick ( = Microcalyptris Braun, Niepeltia Strand), Trifurcula Zeller, Parafomoria Van Nieukerken, Bohemannia Stainton and Ectoedemia Busck in the Trifurculini. Trifurcula is divided into the subgenera Glaucolepis Braun (= Fedalmia Beirne), Levarchama Beirne and Trifurcula s.str. Ectoedemia is divided into the subgenera Etainia Beirne, Fomoria Beirne, Laqueus Scoble, Zimmermannia Hering and Ectoedemia s.str. The genera and subgenera are (re)described and data on biology and distribution are given. The species Simplimorpha promissa (Staudinger) and Acalyptris psammophricta Meyrick are redescribed. A phylogeny of the family in cladistic sense is presented and discussed. The monophyly of Ectoedemia is uncertain, and monophyly of the subgenus Fomoria could not be demonstrated. Current opinions about the phylogenetic position of the Nepticulidae and the division of the Heteroneura are reviewed and discussed. The biogeography and hostplant relationships of the family are reviewed.
Reply

At the outset John Thomas Sanders challenges one of the basic contentions in my overall argument, which is that the steep rise in indirect tax receipts between 1886 and 1900 demonstrates higher rates of peasant consumption, assuming, as modern scholars and contemporaries have done, that the peasants bore the brunt of indirect taxation and that if they paid indirect taxes they must have done some of the consuming. Sanders discards this index by forcefully asserting that there was a difference in consumption between urban and rural dwellers, and that in general peasants did not sustain an improvement in well-being in the 1890s. His argument that "the agrarian peasant was not a major purchaser of the taxed items and that the urban residents of the Russian empire consumed a vastly disproportionate share of the items of 'mass consumption'" strikes me as rather obvious. I have yet to discover in my reading anyone—including myself— who would dispute the fact that the urban sector consumed a larger percentage of consumer goods per capita than the rural sector. By itself this fact tells us nothing about the relative well-being of the peasants or about consumption patterns of rural versus urban dwellers over time. Sanders's data all represent a particular time—1899, 1903, 1911. They do not reflect a comparison of 1886 with 1900, or of 1890 with 1900; that is the critical point in my argument and one of the critical flaws in his use of his data. The standard interpretation of the rural crisis assumes a deterioration of peasant well-being. However imbalanced the difference in consumption between the urban and rural sectors, however much faster urban consumption grew compared to the rate of growth of rural consumption, the question remains: did the per capita consumption of the peasants remain static or increase, to whatever degree, during the last years of the nineteenth century? If it remained static or increased, then the basic historical interpretation of a deterioration of peasant well-being is found wanting. Sanders has not shed any light on this issue at all. To buttress my point, it is pertinent to note that the quotation from I. K. • Ozerov, which Sanders presents to show that urban Russia consumed "some • products ten to twenty times more than the countryside," was written about 1911 and, due to the lack of any evidence to the contrary, apparently pertains to that " particular time period. Despite the overwhelming differential in relative con; sumption cited by Ozerov, there is a consensus among scholars that from 1906
Development of Mucosal PNAd+ and MAdCAM-1+ Venules during Disease Course in Ulcerative Colitis

PNAd and MAdCAM-1 addressins on venules are of importance in T-cell homing and potential therapeutic targets in ulcerative colitis (UC). Normally, PNAd+ high endothelial venules (HEVs) are only present in lymphoid organs, whereas small numbers of MAdCAM-1+ venules can be seen in non-lymphoid tissue. We aimed to study their presence in the intestinal mucosa of UC patients at diagnosis and during follow-up, and their correlation with disease activity. Colonic biopsy specimens of 378 UC patients were analyzed by immunohistochemistry for CD3, CD20, ERG, MECA-79 (PNAd) and MECA-376 (MAdCAM-1) and compared to healthy controls (HC). The proportion of PNAd+HEVs in UC at diagnosis was 4.9% (IQR 2.0%–8.3%), while none were detected in HC. During follow-up, PNAd+HEVs completely disappeared in remission (n = 93), whereas the proportion in active disease was similar to baseline (n = 285, p = 0.39). The proportion of MAdCAM-1+venules in UC at baseline was 5.8% (IQR 2.6–10.0). During follow-up, the proportion in remission was comparable to diagnosis, but upregulated (7.5% (IQR 4.4–10.9), p = 0.001) in active disease. In conclusion, PNAd+HEVs appear in UC during active inflammation which could thus serve as a marker for disease activity, whereas MAdCAM-1+venules remain present after inflammation is resolved and increase after subsequent flares, reflecting chronicity and potentially serving as a therapeutic target.
Development of a neural interface for high-definition, long-term recording in rodents and nonhuman primates

A scalable neural interface technology projected to last at least 6 years in the body samples over a thousand brain sites using flexible electronics. Recording in high resolution Recording large number of neural signals in real time with high definition for long periods of time is necessary for understanding brain physiology and disease pathophysiology. Unfortunately, current brain interface devices only allow recordings of small brain areas with limited number of electrodes. Here, Chiang et al. developed a neural interface device, called Neural Matrix, that allowed stable in vivo neural recordings with high throughput in rodents and nonhuman primates. The system provided stable recordings projected to last for 6 years after implantation. The Neural Matrix will be useful for the study of brain physiology in preclinical setting and might be scalable to humans for clinical purposes. Long-lasting, high-resolution neural interfaces that are ultrathin and flexible are essential for precise brain mapping and high-performance neuroprosthetic systems. Scaling to sample thousands of sites across large brain regions requires integrating powered electronics to multiplex many electrodes to a few external wires. However, existing multiplexed electrode arrays rely on encapsulation strategies that have limited implant lifetimes. Here, we developed a flexible, multiplexed electrode array, called “Neural Matrix,” that provides stable in vivo neural recordings in rodents and nonhuman primates. Neural Matrix lasts over a year and samples a centimeter-scale brain region using over a thousand channels. The long-lasting encapsulation (projected to last at least 6 years), scalable device design, and iterative in vivo optimization described here are essential components to overcoming current hurdles facing next-generation neural technologies.
Differential house finch leukocyte profiles during experimental infection with Mycoplasma gallisepticum isolates of varying virulence

ABSTRACT Leukocyte differentials are a useful tool for assessing systemic immunological changes during pathogen infections, particularly for non-model species. To date, no study has explored how experimental infection with a common bacterial pathogen, Mycoplasma gallisepticum (MG), influences the course and strength of haematological changes in the natural songbird host, house finches. Here we experimentally inoculated house finches with MG isolates known to vary in virulence, and quantified the proportions of circulating leukocytes over the entirety of infection. First, we found significant temporal effects of MG infection on the proportions of most cell types, with strong increases in heterophil and monocyte proportions during infection. Marked decreases in lymphocyte proportions also occurred during infection, though these proportional changes may simply be driven by correlated increases in other leukocytes. Second, we found significant effects of isolate virulence, with the strongest changes in cell proportions occurring in birds inoculated with the higher virulence isolates, and almost no detectable changes relative to sham treatment groups in birds inoculated with the lowest virulence isolate. Finally, we found that variation in infection severity positively predicted the proportion of circulating heterophils and lymphocytes, but the strength of these correlations was dependent on isolate. Taken together, these results indicate strong haematological changes in house finches during MG infection, with markedly different responses to MG isolates of varying virulence. These results are consistent with the possibility that evolved virulence in house finch MG results in higher degrees of immune stimulation and associated immunopathology, with potential direct benefits for MG transmission. RESEARCH HIGHLIGHTS House finches show a marked pro-inflammatory response to M. gallisepticum infection. Virulent pathogen isolates produce stronger finch white blood cell responses. Among birds, stronger white blood cell responses are associated with higher infection severity.
A preliminary study on relationship between arbuscular mycorrhiza fungi and Fusarium wilt of watermelon.

The relationship between arbuscular mycorrhizal fungi (AMF) Gigaspora rosea Nicol. Schenck, Glomus mosseae (Nicol. Gerd.) Gerdemann Trappe, Glomus versiforme (Karsten) Berch and Fusarium wilt ( Fusarium oxysporum f.sp. niveum ) of watermelon was investigated under green house conditions. Results showed that inoculating with AMF were able to increase seedling growth and dry weight of water melon, and significantly reduced the pathogen propagula in roots and the rhizosphere soil, as well as root infection percen tage and disease incidence and disease index. The development of wilt disease was affected by different inoculation time and inoculation sequences of AMF and the pathogen. It was suggested that there was competition between AMF and Fusarium oxysporum f.sp. niveum . In addition, the disease control effects on high susceptible cultivars was greater than those on high resistance cultivars, indicating that the former was more dependent on mycorrhiza.
An insect-plant pathogen interaction between two biocontrol agents, the stem-gall fly and leaf-spot pathogen released against crofton weed, ageratina adenophora

iv TABLE OF CONTENTS vi LIST OF FIGURES x LIST OF TABLES xv CHAPTER 1: INTRODUCTION 1-1 1.1 Background 1-2 1.2 Aims and objectives 1-6 1.2.1 Objectives of the laboratory and field trials 1-7 1.2.2 Objectives of the field surveys 1-7 1.3 Study species 1-9 1.3. 1 Ageratina adenophora 1-9 1.3. 2 Procecidochares utilis 1-11 1.3. 3 Passalora ageratinae 1-12 1.4 Multiple biocontrol agent releases 1-14 1.5 Post-release evaluations 1-17 1.6 Field sites 1-19 1.7 Structure of the thesis 1-21 CHAPTER 2: INTERACTIONS BETWEEN A STEM GALL FLY AND A LEAF-SPOT PATHOGEN IN THE BIOLOGICAL CONTROL OF AGERATINA ADENOPHORA. 2-1 2.1 Abstract 2-2 2.2 Introduction 2-3 2.3 Material and methods 2-6 2.3. 1 Laboratory trials 2-7 2.3. 2 Data analysis 2-10 2.4 Results 2-10 2.4. 1 Impact of AMISTAR ® on Ageratina adenophora growth . 2-10 2.4. 2 Agent establishment and infection severity 2-10 2.4. 3 Stem height 2-13 2.4. 4 Stem growth above the oviposition site 2-13 2.4. 5 Internode length above oviposition site 2-14
Essential hypertension is associated with blunted smooth muscle cell vasodilator responsiveness and is reversed by 10-20-30 training in men.

Essential hypertension is associated with impairments in vascular function and sympathetic nerve hyperactivity; however, the extent to which the lower limbs are affected remains unclear. We examined the leg vascular responsiveness to infusion of acetylcholine (ACh), sodium nitroprusside (SNP) and phenylephrine (PEP) in ten hypertensive men (HYP: age 59.5±9.7 (mean±SD) years, clinical and night-time blood pressure: 142±10/86±10 and 141±11/83±6 mmHg, respectively, BMI: 29.2±4.0 kg∙m-2) and 8 age-matched normotensive counterparts (NORM: age 57.9±10.8 years, clinical and night-time blood pressure: 128±9/78±7 and 116±3/69±3 mmHg, respectively, BMI: 26.3±3.1 kg∙m-2). The vascular responsiveness was evaluated before and after 6 weeks of 10-20-30 training, consisting of 3x 5x10-s sprint followed by 30 and 20 s of low- to moderate-intensity cycling, respectively, interspersed by 3 min of rest. Before training, the vascular responsiveness to infusion of SNP was lower (P<0.05) in HYP compared to NORM, with no difference in the responsiveness to infusion of ACh and PEP. The vascular responsiveness to infusion of SNP and ACh improved (P<0.05) with training in HYP, with no change in NORM. With training, intra-arterial systolic blood pressure decreased (P<0.05) by 9 mmHg in both HYP and NORM whereas diastolic blood pressure decreased (5 mmHg; P<0.05) in HYP only. We provide here the first line of evidence in humans that smooth muscle cell vasodilator responsiveness is blunted in the lower limbs of hypertensive men. This impairment can be reversed by 10-20-30 training, which is an effective intervention to improve the responsiveness of smooth muscle cells in men with essential hypertension.
Scrambler therapy improves pain in neuromyelitis optica

Objective To determine whether Scrambler therapy is an effective, acceptable, and feasible treatment of persistent central neuropathic pain in patients with neuromyelitis optica spectrum disorder (NMOSD) and to explore the effect of Scrambler therapy on co-occurring symptoms. Methods We conducted a randomized single-blind, sham-controlled trial in patients with NMOSD who have central neuropathic pain using Scrambler therapy for 10 consecutive weekdays. Pain severity, pain interference, anxiety, depression, and sleep disturbance were assessed at baseline, at the end of treatment, and at the 30- and 60-day follow-up. Results Twenty-two patients (11 per arm) were enrolled in and completed this trial. The median baseline numeric rating scale (NRS) pain score decreased from 5.0 to 1.5 after 10 days of treatment with Scrambler therapy, whereas the median NRS score did not significantly decrease in the sham arm. Depression was also reduced in the treatment arm, and anxiety was decreased in a subset of patients who responded to treatment. These symptoms were not affected in the sham arm. The safety profiles were similar between groups. Conclusions Scrambler therapy is an effective, feasible, and safe intervention for central neuropathic pain in patients with NMOSD. Decreasing pain with Scrambler therapy may additionally improve depression and anxiety. Clinicaltrials.gov identifier NCT03452176. Classification of evidence This study provides Class II evidence that Scrambler therapy significantly reduces pain in patients with NMOSD and persistent central neuropathic pain.
Prevalence and types of bacterial infections of the upper respiratory tract at a tertiary care hospital in the City of Tripoli

Aim: The study aimed to determine the bacterial etiology of upper tract respiratory infection in Abu-Sitta Hospital, Tripoli, Libya. Subjects and Methods: A total of 470 sputum specimens and 60 throat swabs were collected over a period of 1 year (From January 2014 to December 2014) from patients presented with clinical signs of upper respiratory tract infection at Abu-Sitta Hospital. Enrolled patients were sorted as inpatients or outpatients and by gender. Data were entered and analyzed using SPSS version 22.0. Variables were expressed as percentages. Differences in age and gender were analyzed using Chi-square test. Results: Of the total 530 screened samples, 80.5% were culture positive, where bacterial pathogens were detected in 83.7% of sputum specimens and in 56.5% of throat swabs. Streptococcus pneumoniae was the most prevalent (48%), followed by Pseudomonas aeruginosa (23%), Staphylococcus aureus (13%), Enterobacter (8%), Citrobacter freundil (5%), and latest with Klebsiella (3%). Conclusions: The spectrum of pathogenic bacterium causing upper respiratory infection in Abu-Sitta Hospital is considerably wide, with S. pneumoniae and P. aeruginosa being the major causative bacteria.