Lovemclaughlin0934

We describe two unrelated Indian boys with Mental retardation with language impairment with or without autistic features (OMIM#613670). Novel pathogenic variants c. 593_599 delins AGAAG and c.1556T>C in FOXP1 were identified in Patients 1 and 2, respectively by exome sequencing. The patients shared the cardinal features of significant language impairment, prominent forehead, downslanted palpebral fissures, frontal upsweep of hair, and behavioral abnormalities. Camptodactyly (with pterygia in Patient 2) was an additional feature noted in our study. The phenotype was consistent with previous reports of patients with monogenic defects in FOXP1. The facial features overlap with Sotos syndrome. However, presence of frontal upsweep of hair is a good pointer toward FOXP1 related syndromic intellectual disability.Cancer chemotherapy typically relies on drug endocytosis and inhibits tumor cell proliferation via intracellular pathways; however, severe side effects may arise. In this study, we performed a first attempt to develop macromolecular-induced extracellular chemotherapy involving biomineralization by absorbing calcium from the blood through a new type of drug, polysialic acid conjugated with folate (folate-polySia), which selectively induces biogenic mineral formation on tumor cells and results in the pathological calcification of tumors. The macromolecule-initiated extracellular calcification causes cancer cell death mainly by intervening with the glycolysis process in cancer cells. Systemic administration of folate-polySia inhibited cervical and breast tumor growth and dramatically improved survival rates in mice. This study provides an extracellular therapeutic approach for malignant tumor diseases via calcification that is ready for clinical trials and offers new insights into macromolecular anticancer drug discovery.Social insects are notable for having two female castes that exhibit extreme differences in their reproductive capacity. The molecular basis of these differences is largely unknown. Vitellogenin (Vg) is a powerful antioxidant and insulin-signalling regulator used in oocyte development. Here we investigate how Royal Jelly (the major food of honeybee queens) and queen mandibular pheromone (a major regulator of worker fertility), affect the longevity and reproductive status of honey bee workers, the expression of Vg, its receptor VgR and associated regulatory proteins. We find that Vg is expressed in the ovaries of workers and that workers fed a queen diet of Royal Jelly have increased Vg expression in the ovaries. Surprisingly, we find that expression of Vg is not associated with ovary activation in workers, suggesting that this gene has potentially acquired non-reproductive functions. Therefore, Vg expression in the ovaries of honeybee workers provides further support for the Ovarian Ground Plan Hypothesis, which argues that genes implicated in the regulation of reproduction have been co-opted to regulate behavioural differences between queens and workers.The AlI compound NacNacAl (1, NacNac = [ArNC(Me)CHC(Me)NAr]- , Ar = 2,6-iPr2 C6 H3 ) serves as a template for the chemoselective coupling between carbonyls (benzophenone, fenchone, isophorone, p-tolyl benzoate, N,N-dimethylbenzamide, (1-phenylethylidene)aniline) and pyridine. With the CH-acidic ketone (1R)-(+) camphor, the reaction affords a hydrido alkoxide compound of Al, formed as the result of enolization, whereas an enolizable imine, (1-phenylethylidene)aniline, and the bulky ketone isophorone, still chemoselectively couple with pyridine. In contrast, reaction with the ester p-tolyl benzoate results in cleavage of the ester bond together with replacement of the alkoxy group by a hydrogen atom of the pyridine moiety. This study demonstrates that for carbonyl substrates featuring phenyl substituents, the reaction proceeds via intermediate formation of η2 (C,X)-coordinated (X = O, N) carbonyl adducts, whereas the reaction of 1 with (R)-(-)-fenchone in the absence of pyridine leads to CH activation in the pendant isopropyl group of the Ar substituent of the NacNac ligand.Although doped poly(3,4-ethylenedioxythiophene) (PEDOT) is extensively used in electronic devices, their molecular-weight distributions and inadequately defined structures have hindered the elucidation of their underlying conduction mechanism. In this study, we introduce the simplest discrete oligomer models EDOT dimer radical cation salts. Single-crystal structural analyses revealed their one-dimensional (1D) columnar structures, in which the donors were uniformly stacked. Band calculations identified 1D metallic band structures with a strong intracolumnar orbital interaction (band width W≈1 eV), implying the origin of the high conductivity of doped PEDOT. Interestingly, the salts exhibited semiconducting behavior reminiscent of genuine Mott states as a result of electron-electron repulsion (U) dominant over W. This study realized basic models with tunable W and U to understand the conduction mechanism of doped PEDOT through structural modification in oligomers, including the conjugation length.A liquescent dihydrophenazine radical cation, 1.+ ⋅NTf2 - , showed drastic changes in near-infrared (near-IR) transparency and opaqueness through hysteretic phase transitions with no measurable degradation of the compound even under aerated conditions. During the heating and slow cooling process (0.5 K min-1 ), its electronic and magnetic properties were altered clearly and repeatedly changed between solid and liquid states. The liquid state was transparent to near-IR light (940 nm), but the solid state was opaque, despite both samples exhibiting a similar green color under room light. Additionally, the liquid state was changed to a glass state under a fast cooling process (2-10 K min-1 ). UV/Vis/near-IR and electron spin-resonance spectroscopy revealed that these drastic changes were attributable to the dynamic dissociation and association of a π-dimer structure for 1.+ accompanying with the solid-liquid phase transitions even under the neat conditions.The evolution of form and function of trees of diverse species has taken place over hundreds of millions of years, while urban environments are relatively new on an evolutionary time scale, representing a novel set of environmental constraints for trees to respond to. It is important to understand how trees of different species, planted in these anthropogenically-structured urban ecosystems, are responding to them. Many theories have been advanced to understand tree form and function, including several that suggest the fractal-like geometry of trees is a direct reflection of inherent and plastic morphological and physiological traits that govern tree growth and survival. In this research, we analyzed the "fractal dimension" of thousands of tree crowns of many different tree species, growing in different urban environments across the United States, to learn more about the nature of trees and their responses to urban environments at different scales. Our results provide new insights regarding how tree crown fraes, worldwide, our results add new insights into the physiological ecology of trees in urban environments, which may help humans to provide more hospitable habitats for trees in urbanized areas and to make better decisions about tree selection in urban forest management.

Early tacrolimus (TAC) concentrations correlate with the risk of acute graft-versus-host disease (aGVHD); however, whether the variability of early TAC concentrations after allo-HSCT governs the occurrence of aGVHD remains unknown. Here, we evaluate the correlation between the intrapatient variability (IPV) of initial TAC concentrations and the development of aGVHD.

We retrospectively assessed 202 patients who underwent allo-HSCT and received standard GVHD prophylaxis by continuous intravenous (iv) infusion of TAC and iv methotrexate. IPV was calculated by using the % coefficient of variation in the initial 4weeks.

With median follow-up duration of 20.7months, 24 patients were diagnosed with grades II-IV aGVHD. Overall survival (OS) and relapse at 12months after allo-HSCT were 70.6% (95% confidence interval [CI], 63.7%-76.4%) and 18.9% (95% CI, 13.0%-24.4%), respectively. When IPV was categorized into two groups (high ≥9.5%; low <9.5%), the cumulative incidence of grades II-IV aGVHD was greater in the IPV-high group at week 3 (odds ratio 4.15; 95% CI, 1.37%-12.6%, P=.01). No significant differences were observed in OS and relapse between the two groups.

We concluded that adjusting early TAC concentration stable may reduce aGVHD after allo-HSCT without affecting the relapse rate.

We concluded that adjusting early TAC concentration stable may reduce aGVHD after allo-HSCT without affecting the relapse rate.Xenobiology explores synthetic nucleic acid polymers as alternative carriers of genetic information to expand the central dogma. The xylo- and deoxyxylo-nucleic acids (XyNA and dXyNA), containing 3' epimers of riboses and deoxyriboses, are considered to be potential candidates for an orthogonal system. In this study, thermal and spectroscopic analyses show that XyNA and dXyNA form stable hairpins. The dXyNA hairpin structure determined by NMR spectroscopy contains a flexible loop that locks the stem into a stable ladder-like duplex with marginal right-handed helicity. The reduced flexibility of the dXyNA duplex observed in the stem of the hairpin demonstrates that folding of dXyNA yields more stable structures described so far.Three new cadmium-based coordination polymers, denoted [Cd(hfipbb)(4,4'-bipy)] (CdPF-1), [Cd(hfipbb)(2,2'-bipy)] (CdPF-2), and [Cd(hfipbb)(1,10-phen)] (CdPF-3), have been hydrothermally synthesized by using the well-known V-shaped organic linker 4,4'-(hexafluoroisopropylidene)bis(benzoic acid) (H2 hfipbb), together with different nitrogenated auxiliary linkers. find more Considering the d10 configuration of the transition metal selected, the luminescent properties for these CdPF-n materials were explored, finding that materials CdPF-2 and CdPF-3 act as excellent sensors in the detection of explosive nitro aromatic compounds. The photoluminescence properties of CdPF-2 and CdPF-3 revealed that significant and sensitive fluorescence quenching was observed toward NP (nitrophenol) for CdPF-2 and PA (picric acid) for CdPF-3 in MeOH suspensions.

Smoking status at point of diagnosis is not used in defining risk groups for human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) despite its prognostic value in head and neck cancer.

Retrospective analysis of consecutive patients treated with chemoradiotherapy between January 2005 and July 2017 was performed with multivariable analysis to explore the impact of smoking status at diagnosis (current/former/never) on overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS).

Median follow-up was 61 months. Four hundred and four patients were included. Current smokers had inferior OS versus never and former smokers [adjusted HR 2.37 (95% CI 1.26-4.45, p < 0.01) and 2.58 (95% CI 1.40-4.73, p < 0.01), respectively] and inferior PFS versus never smokers [adjusted HR 1.83 (95% CI 1.00-3.35, p = 0.04)]. Smoking status did not predict for CSS.

Detailed smoking behavior should be considered in refining risk groups in HPV-associated OPC treated with radiotherapy and in future trial design eligibility and stratification.