The loss of dopamine (DA) neurons within the substantia nigra pars compacta (SNpc) is a defining pathological hallmark of Parkinson's disease (PD). Nevertheless, the molecular features associated ...with DA neuron vulnerability have not yet been fully identified. Here, we developed a protocol to enrich and transcriptionally profile DA neurons from patients with PD and matched controls, sampling a total of 387,483 nuclei, including 22,048 DA neuron profiles. We identified ten populations and spatially localized each within the SNpc using Slide-seq. A single subtype, marked by the expression of the gene AGTR1 and spatially confined to the ventral tier of SNpc, was highly susceptible to loss in PD and showed the strongest upregulation of targets of TP53 and NR2F2, nominating molecular processes associated with degeneration. This same vulnerable population was specifically enriched for the heritable risk associated with PD, highlighting the importance of cell-intrinsic processes in determining the differential vulnerability of DA neurons to PD-associated degeneration.
Background
Gastroschisis is an abdominal wall defect with potential devastating outcomes, including short bowel syndrome (SBS). The objective of this study is to define current practices in prenatal ...gastroschisis surveillance.
Methods
An online survey was circulated to the Society for Maternal Fetal Medicine (SMFM) providers. Questions focused on timing, type, and frequency of surveillance, proposed interventions, and the impact of gastroschisis defect diameter on plan of care.
Results
Responses were obtained from 150/1104 (14%) SMFM providers. The majority of respondents worked in practices in an academic setting (61%) and more than half (58%) had been in maternal fetal medicine (MFM) practice for > 10 years. Antenatal testing began at 32 weeks for 78% of MFM providers. Surveillance was unanimously uniformly performed with ultrasound. About 40% of the providers would consider all abnormalities in the measured parameters to change their surveillance frequency. In non-complicated gastroschisis, 44% of the providers would recommend delivery at 37 weeks of gestational age, with the vast majority of them (96%) recommending vaginal delivery. Among the 23% who expressed their thoughts, 70% agreed that a smaller defect size correlated with the higher risk for development of SBS. Nevertheless, only 2% declared an absolute cutoff point (< 8 mm–3 cm) at which they would recommend delivery. Only one-fifth of the participants (21%) noted that the abdominal wall defect size has an impact on development of SBS. A higher percentage of SMFM providers (89%) with ≤ 10 years of experience started the antenatal testing at week 32 weeks compared to 66% of senior providers. Senior providers were more inclined (50%) to induce labor at 37 weeks compared to SMFM providers with > 10 years of experience (38%).
Conclusions
Gastroschisis management does not differ dramatically among SMFM providers, though noticeable differences in surveillance and timing of induction were identified based on years of experience as providers. The impact of gastroschisis defect dimensions on development of SBS may be under appreciated.
Hematopoietic stem-cell transplantation (HSCT) is the most potent curative therapy for many malignant and non-malignant disorders. Unfortunately, a major complication of HSCT is graft-versus-host ...disease (GVHD), which is mediated by tissue damage resulting from the conditioning regimens before the transplantation and the alloreaction of dual immune components (activated donor T-cells and recipient's antigen-presenting cells). This tissue damage leads to the release of alarmins and the triggering of pathogen-recognition receptors that activate the innate immune system and subsequently the adaptive immune system. Alarmins, which are of endogenous origin, together with the exogenous pathogen-associated molecular patterns (PAMPs) elicit similar responses of danger signals and represent the group of damage-associated molecular patterns (DAMPs). Effector cells of innate and adaptive immunity that are activated by PAMPs or alarmins can secrete other alarmins and amplify the immune responses. These complex interactions and loops between alarmins and PAMPs are particularly potent at inducing and then aggravating the GVHD reaction. In this review, we highlight the role of these tissue damaging molecules and their signaling pathways. Interestingly, some DAMPs and PAMPs are organ specific and GVHD-induced and have been shown to be interesting biomarkers. Some of these molecules may represent potential targets for novel therapeutic approaches.
Cellular automata (CA) are self-organizing lattices consisting of cell grids, and the state of each cell can be updated according to the neighboring cell states. The updating rules depend on the ...neighbors involved in updating a particular cell. In a two-dimensional CA (2DCA) structure, each cell has nine neighbors, including the cell itself. The CA characteristics may change depending on the nature of the operations and the set of neighbors used. Accordingly, researchers have used the 2DCA group rules as a tool to model complex systems in various applications, including artificial intelligence, genomics, computer architecture, graphics, image processing, engineering, and physics. However, nongroup 2DCA rules contain a large number of rules, and the general behavior of all these rules has not yet been studied. In this study, the behavior of 2DCA nongroup rules with null boundary conditions was investigated, and the rules were classified into three categories based on their cycle length and depth. In addition, we applied these classifications to propose a cellular automata-based pseudo-random number generator (PRNG). Statistical tests were performed to validate the suitability of the nongroup CA rules for PRNGs.
This research aimed to survey the insect pollinators and visitors of canola, to assay their foraging activities and to study their effects on three canola cultivars (Pactol, Serw-4 and Serw-6) at the ...Experimental Field Station in Assiut region, Upper Egypt during two flowering seasons 2017/18 and 2018/19. The results manifested that there were nine species of insect pollinators and visitors belonging to four orders and eight families. The majority of the pollinators were Hymenoptera (83%), especially honey bees (Apis mellifera L.), Diptera (12%), Butterflies (Lepidoptera; 3%) and the beetles (Coleoptera; 2%). The peak activity of honey bees was recorded between 9 am and 11 am while for the other insect pollinators, except, syrphid flies was 11 am. The caged cultivars (without insect pollination) had statistically significant lower yield parameters (silique number per plant, seed number per silique, weight of 1000 seeds, oil content and seed germination) than the uncaged cultivars (accessible to insect pollinators and visitors). Uncaged plants of canola Pactol and Serw-4 cultivars had high seed oil content (44.34, 51.40%), seed yield (681.8, 429.0 kg/ha.) and seed germination percentage (80, 86%), respectively. Serw-4 cultivar had the first rank in the weight of siliques and seeds. This study indicated that the yield of the canola crop was positively influenced by insect pollinators. Serw-4 is a promising cultivar for large-scale production of edible oil.
Herbicides are the most frequently used pesticides, accounting for more than 60% of all pesticides used in agriculture around the world. Clethodim (CTD) (Vixtol Super
®
24% EC), haloxyfop-p-methyl ...(HFM) (Gallant Super
®
10.8% EC), and their mixture (CTD (15%) + HFM (7.5%) (Fine
®
22.5% EC) are among the most commonly used post-emergence graminicides in Egypt and worldwide. However, little data on their toxicological effects on honey bees (
Apis mellifera
L.) is known. In this study, the lethal and sublethal effects of CTD or HFM and their mixture were assessed in the laboratory on foragers and nurse honey bee workers, respectively. In the acute toxicity test, HFM was more toxic to forager workers (LC
50
= 0.95 mg a.i./ml) after 96 h of oral exposure, followed by CTD then the mixture which was the least toxic one. In a chronic toxicity test, newly emerged bees were fed sugar syrup that was herbicide-free (control) or sugar syrup that contained a sublethal concentration of HFM (0.2 mg/ml; 1/5 of 96 h-LC
50
) or CTD (0.6 mg/ml; 1/5 96 h-LC
50
) or the mixture (0.2 mg/ml; 1/15 96 h-LC
50
) for 20 days. CTD significantly reduced bee survival and dry body weight compared to non-exposed control bees and bees exposed to HFM or the mixture. Chronic sublethal exposure to these herbicides also caused a considerable reduction in hypopharyngeal glan (HPG) acini volume, severe morphologic alterations, and a deleterious impact on hemocyte account and differentiation. This is the first study of its kind to indicate that herbicides that inhibit acetyl-CoA-carboxylase (ACCase) have a negative impact on honey bee health at sublethal levels.
Delusional infestation (DI) describes a fixed, false belief where a person believes that they are infested with living or inanimate pathogens despite the absence of medical evidence for such ...infestation. Descriptions of alleged pathogens have evolved over time, incorporating inanimate objects such as fibrous strands. With the emergence of Morgellons disease and its controversy, we report a case of a 40-year-old female presenting with a strong belief of scabies infestation along with fibers emerging from her skin. Further, although insects are still the most alleged source of infestation, the overlap of Morgellons disease and the delusion of infestation supports it as a DI variant and questions the notion of its existence as a separate diagnostic entity.
This study aimed to evaluate the antioxidant activity and total phenolic content (TPC) and total flavonoid content (TFC) of crude extracts obtained from three
species, namely,
L.,
L., and
(Forsk.) ...Decne. Both butanol and aq. methanol extracts of the three species showed the highest amount of phenol and flavonoid contents, which exhibited the greatest antioxidant activity in the scavenging of 2,2-diphenyl-2-picrylhydrazyl free radical (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation (ABTS), ferrous chelating effect (FIC), and hydroxyl radical (HDR) assays. Phytochemical screening of the extracts revealed the presence of alkaloids, tannins, sponins, flavonoids, terpenoids, and glycosides. LC-MS analysis was carried out to identify the major compounds from each crude extract. A total of 12 phenolic compounds in the extracts of the 3 species were identified and quantified, including 9 flavonoids, 2 hydroxybenzoic acids, and 3 hydroxycinnamic acids. The current study also revealed a good correlation between total phenolic contents and the observed antioxidant activity of the crude extracts.
Graft-versus-host disease (GVHD) remains a devastating complication after allogeneic hematopoietic cell transplantation (HCT). We previously identified high plasma soluble suppression of ...tumorigenicity 2 (sST2) as a biomarker of the development of GVHD and death. sST2 sequesters interleukin-33 (IL-33), limiting its availability to T cells expressing membrane-bound ST2 (mST2) T helper 2 (TH2) cells and ST2(+)FoxP3(+) regulatory T cells. We report that blockade of sST2 in the peritransplant period with a neutralizing monoclonal antibody (anti-ST2 mAb) reduced GVHD severity and mortality. We identified intestinal stromal cells and T cells as major sources of sST2 during GVHD. ST2 blockade decreased systemic interferon-γ, IL-17, and IL-23 but increased IL-10 and IL-33 plasma levels. ST2 blockade also reduced sST2 production by IL-17-producing T cells while maintaining protective mST2-expressing T cells, increasing the frequency of intestinal myeloid-derived suppressor cells, and decreasing the frequency of intestinal CD103 dendritic cells. Finally, ST2 blockade preserved graft-versus-leukemia activity in a model of green fluorescent protein (GFP)-positive MLL-AF9 acute myeloid leukemia. Our findings suggest that ST2 is a therapeutic target for severe GVHD and that the ST2/IL-33 pathway could be investigated in other T cell-mediated immune disorders with loss of tolerance.
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