Direct Access to Unnatural Cyclobutane ?-Amino Acids through Visible Light Catalyzed [2+2]-Cycloaddition

In this work, we report the first selective, photocatalyzed [2+2]-cycloaddition of dehydroamino acids with styrene-type olefins. This simple, mild, and scalable approach relies on the use of the triplet energy transfer catalyst [Ir(dFCF(3)ppy(2))dtbpy]PF6 under visible light irradiation and provides fast access to value-added substituted strained cyclobutane alpha-amino acid derivatives. © 2022 The Authors. Published by American Chemical Society

More anxious than depressed: prevalence and correlates in a 15-nation study of anxiety disorders in people with type 2 diabetes mellitus

Background Anxiety disorder, one of the highly disabling, prevalent and common mental disorders, is known to be more prevalent in persons with type 2 diabetes mellitus (T2DM) than the general population, and the comorbid presence of anxiety disorders is known to have an impact on the diabetes outcome and the quality of life. However, the information on the type of anxiety disorder and its prevalence in persons with T2DM is limited. Aims To assess the prevalence and correlates of anxiety disorder in people with type 2 diabetes in different countries. Methods People aged 18–65 years with diabetes and treated in outpatient settings were recruited in 15 countries and underwent a psychiatric interview with the Mini-International Neuropsychiatric Interview. Demographic and medical record data were collected. Results A total of 3170 people with type 2 diabetes (56.2% women; with mean (SD) duration of diabetes 10.01 (7.0) years) participated. The overall prevalence of anxiety disorders in type 2 diabetic persons was 18%; however, 2.8% of the study population had more than one type of anxiety disorder. The most prevalent anxiety disorders were generalised anxiety disorder (8.1%) and panic disorder (5.1%). Female gender, presence of diabetic complications, longer duration of diabetes and poorer glycaemic control (HbA1c levels) were significantly associated with comorbid anxiety disorder. A higher prevalence of anxiety disorders was observed in Ukraine, Saudi Arabia and Argentina with a lower prevalence in Bangladesh and India. Conclusions Our international study shows that people with type 2 diabetes have a high prevalence of anxiety disorders, especially women, those with diabetic complications, those with a longer duration of diabetes and poorer glycaemic control. Early identification and appropriate timely care of psychiatric problems of people with type 2 diabetes is warranted

Orbital effects of a monochromatic plane gravitational wave with ultra-low frequency incident on a gravitationally bound two-body system

We analytically compute the long-term orbital variations of a test particle orbiting a central body acted upon by an incident monochromatic plane gravitational wave. We assume that the characteristic size of the perturbed two-body system is much smaller than the wavelength of the wave. Moreover, we also suppose that the wave's frequency is much smaller than the particle's orbital one. We make neither a priori assumptions about the direction of the wavevector nor on the orbital geometry of the planet. We find that, while the semi-major axis is left unaffected, the eccentricity, the inclination, the longitude of the ascending node, the longitude of pericenter and the mean anomaly undergo non-vanishing long-term changes. They are not secular trends because of the slow modulation introduced by the tidal matrix coefficients and by the orbital elements themselves. They could be useful to indepenedently constrain the ultra-low frequency waves which may have been indirectly detected in the BICEP2 experiment. Our calculation holds, in general, for any gravitationally bound two-body system whose characteristic frequency is much larger than the frequency of the external wave. It is also valid for a generic perturbation of tidal type with constant coefficients over timescales of the order of the orbital period of the perturbed particle.Comment: LaTex2e, 24 pages, no figures, no tables. Changes suggested by the referees include

The Efficacy of Generating Three Independent Anti-HIV-1 siRNAs from a Single U6 RNA Pol III-Expressed Long Hairpin RNA

RNA Interference (RNAi) effectors have been used to inhibit rogue RNAs in mammalian cells. However, rapidly evolving sequences such as the human immunodeficiency virus type 1 (HIV-1) require multiple targeting approaches to prevent the emergence of escape variants. Expressed long hairpin RNAs (lhRNAs) have recently been used as a strategy to produce multiple short interfering RNAs (siRNAs) targeted to highly variant sequences. We aimed to characterize the ability of expressed lhRNAs to generate independent siRNAs that silence three non-contiguous HIV-1 sites by designing lhRNAs comprising different combinations of siRNA-encoding sequences. All lhRNAs were capable of silencing individual target sequences. However, silencing efficiency together with concentrations of individual lhRNA-derived siRNAs diminished from the stem base (first position) towards the loop side of the hairpin. Silencing efficacy against HIV-1 was primarily mediated by siRNA sequences located at the base of the stem. Improvements could be made to first and second position siRNAs by adjusting spacing arrangements at their junction, but silencing of third position siRNAs remained largely ineffective. Although lhRNAs offer advantages for combinatorial RNAi, we show that good silencing efficacy across the span of the lhRNA duplex is difficult to achieve with sequences that encode more than two adjacent independent siRNAs

A common toxin fold mediates microbial attack and plant defense

Many plant pathogens secrete toxins that enhance microbial virulence by killing host cells. Usually, these toxins are produced by particular microbial taxa, such as bacteria or fungi. In contrast, many bacterial, fungal and oomycete species produce necrosis and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) that trigger leaf necrosis and immunity-associated responses in various plants. We have determined the crystal structure of an NLP from the phytopathogenic oomycete Pythium aphanidermatum to 1.35Å resolution. The protein fold exhibits structural similarities to cytolytic toxins produced by marine organisms (actinoporins). Computational modeling of the 3-dimensional structure of NLPs from another oomycete, Phytophthora parasitica, and from the phytopathogenic bacterium, Pectobacterium carotovorum, revealed a high extent of fold conservation. Expression of the 2 oomycete NLPs in an nlp-deficient P. carotovorum strain restored bacterial virulence, suggesting that NLPs of prokaryotic and eukaryotic origins are orthologous proteins. NLP mutant protein analyses revealed that identical structural properties were required to cause plasma membrane permeabilization and cytolysis in plant cells, as well as to restore bacterial virulence. In sum, NLPs are conserved virulence factors whose taxonomic distribution is exceptional for microbial phytotoxins, and that contribute to host infection by plasma membrane destruction and cytolysis. We further show that NLP-mediated phytotoxicity and plant defense gene expression share identical fold requirements, suggesting that toxin-mediated interference with host integrity triggers plant immunity-associated responses. Phytotoxin-induced cellular damage-associated activation of plant defenses is reminiscent of microbial toxin-induced inflammasome activation in vertebrates and may thus constitute another conserved element in animal and plant innate immunity