Oxidative Coupling with Zr(IV) Supported by a Noninnocent Anthracene-Based Ligand: Application to the Catalytic Cotrimerization of Alkynes and Nitriles to Pyrimidines

We report the synthesis and reactivity of Zr complexes supported by a 9,10-anthracenediyl-linked bisphenoxide ligand, L. Zr^(IV)LBn_2 (1) undergoes facile photolytic reduction with concomitant formation of bibenzyl and Zr^(IV)L(THF)_3 (2), which displays a two-electron reduced anthracene moiety. Leveraging ligand-stored reducing equivalents, 2 promotes the oxidative coupling of internal and terminal alkynes to isolable zirconacyclopentadiene complexes, demonstrating the reversible utilization of anthracene as a redox reservoir. With diphenylacetylene under CO, cyclopentadienone is formed stoichiometrically. 2 is competent for the catalytic formation of pyrimidines from alkynes and nitriles. Mechanistic studies suggest that selectivity for pyrimidine originates from preferred formation of an azazirconacyclopentadiene intermediate, which reacts preferentially with nitriles over alkynes

Human endogenous retrovirus K106 (HERV-K106) was infectious after the emergence of anatomically modern humans.

HERV-K113 and HERV-K115 have been considered to be among the youngest HERVs because they are the only known full-length proviruses that are insertionally polymorphic and maintain the open reading frames of their coding genes. However, recent data suggest that HERV-K113 is at least 800,000 years old, and HERV-K115 even older. A systematic study of HERV-K HML2 members to identify HERVs that may have infected the human genome in the more recent evolutionary past is lacking. Therefore, we sought to determine how recently HERVs were exogenous and infectious by examining sequence variation in the long terminal repeat (LTR) regions of all full-length HERV-K loci. We used the traditional method of inter-LTR comparison to analyze all full length HERV-Ks and determined that two insertions, HERV-K106 and HERV-K116 have no differences between their 5' and 3' LTR sequences, suggesting that these insertions were endogenized in the recent evolutionary past. Among these insertions with no sequence differences between their LTR regions, HERV-K106 had the most intact viral sequence structure. Coalescent analysis of HERV-K106 3' LTR sequences representing 51 ethnically diverse individuals suggests that HERV-K106 integrated into the human germ line approximately 150,000 years ago, after the emergence of anatomically modern humans

Formation of Alkanes by Aerobic Carbon–Carbon Bond Coupling Reactions Catalyzed by a Phosphovanadomolybdic Acid

The valorization of alkanes is possible via carbon–carbon coupling reactions. A series of dialkyl cobalt complexes [(RCH_2)_2Co^(III)(bpy)_2]ClO_4 (R = H, Me, Et, and Ph) were reacted with the H_5PV_2Mo_(10)O_(40) polyoxometalate as a catalyst, leading to a selective oxidative carbon–carbon bond coupling reaction. The reaction is initiated by electron transfer from [(RCH_2)_2Co^(III)(bpy)_2]^+ to H_5PV^V_2Mo_(10)O_(40) to yield an intermediate [(RCH_2)_2Co^(IV)(bpy)_2]^(2+)–H_5PV^(IV)V^VMo_(10)O_(40), as identified by a combination of EPR and X-ray photoelectron spectroscopy experiments. The reaction is catalytic with O_2 as terminal oxidant representing an aerobic C–C bond coupling reaction

Human Endogenous Retrovirus K106 (HERV-K106) Was Infectious after the Emergence of Anatomically Modern Humans

HERV-K113 and HERV-K115 have been considered to be among the youngest HERVs because they are the only known full-length proviruses that are insertionally polymorphic and maintain the open reading frames of their coding genes. However, recent data suggest that HERV-K113 is at least 800,000 years old, and HERV-K115 even older. A systematic study of HERV-K HML2 members to identify HERVs that may have infected the human genome in the more recent evolutionary past is lacking. Therefore, we sought to determine how recently HERVs were exogenous and infectious by examining sequence variation in the long terminal repeat (LTR) regions of all full-length HERV-K loci. We used the traditional method of inter-LTR comparison to analyze all full length HERV-Ks and determined that two insertions, HERV-K106 and HERV-K116 have no differences between their 5′ and 3′ LTR sequences, suggesting that these insertions were endogenized in the recent evolutionary past. Among these insertions with no sequence differences between their LTR regions, HERV-K106 had the most intact viral sequence structure. Coalescent analysis of HERV-K106 3′ LTR sequences representing 51 ethnically diverse individuals suggests that HERV-K106 integrated into the human germ line approximately 150,000 years ago, after the emergence of anatomically modern humans.</p

Pre-hospital management protocols and perceived difficulty in diagnosing acute heart failure

Aim To illustrate the pre-hospital management arsenals and protocols in different EMS units, and to estimate the perceived difficulty of diagnosing suspected acute heart failure (AHF) compared with other common pre-hospital conditions. Methods and results A multinational survey included 104 emergency medical service (EMS) regions from 18 countries. Diagnostic and therapeutic arsenals related to AHF management were reported for each type of EMS unit. The prevalence and contents of management protocols for common medical conditions treated pre-hospitally was collected. The perceived difficulty of diagnosing AHF and other medical conditions by emergency medical dispatchers and EMS personnel was interrogated. Ultrasound devices and point-of-care testing were available in advanced life support and helicopter EMS units in fewer than 25% of EMS regions. AHF protocols were present in 80.8% of regions. Protocols for ST-elevation myocardial infarction, chest pain, and dyspnoea were present in 95.2, 80.8, and 76.0% of EMS regions, respectively. Protocolized diagnostic actions for AHF management included 12-lead electrocardiogram (92.1% of regions), ultrasound examination (16.0%), and point-of-care testings for troponin and BNP (6.0 and 3.5%). Therapeutic actions included supplementary oxygen (93.2%), non-invasive ventilation (80.7%), intravenous furosemide, opiates, nitroglycerine (69.0, 68.6, and 57.0%), and intubation 71.5%. Diagnosing suspected AHF was considered easy to moderate by EMS personnel and moderate to difficult by emergency medical dispatchers (without significant differences between de novo and decompensated heart failure). In both settings, diagnosis of suspected AHF was considered easier than pulmonary embolism and more difficult than ST-elevation myocardial infarction, asthma, and stroke. Conclusions The prevalence of AHF protocols is rather high but the contents seem to vary. Difficulty of diagnosing suspected AHF seems to be moderate compared with other pre-hospital conditions

Coming Back to Life: The Permeability of Past and Present, Mortality and Immortality, Death and Life in the Ancient Mediterranean

The lines between death and life were neither fixed nor finite to the peoples of the ancient Mediterranean. For most, death was a passageway into a new and uncertain existence. The dead were not so much extinguished as understood to be elsewhere, and many perceived the deceased to continue to exercise agency among the living. Even for those more skeptical of an afterlife, notions of coming back to life provided frameworks in which to conceptualize the on-going social, political, and cultural influence of the past. This collection of essays examines how notions of coming back to life shape practices and ideals throughout the ancient Mediterranean. All contributors focus on the common theme of coming back to life as a discursive and descriptive space in which antique peoples construct, maintain, and negotiate the porous boundaries between past and present, mortality and immortality, death and life

Expanding the horizon of research into the pathogenesis of the white matter diseases: Proceedings of the 2021 Annual Workshop of the Albert Research Institute for White Matter and Cognition

White matter pathologies are critically involved in the etiology of vascular cognitive impairment–dementia (VCID), Alzheimer’s disease (AD), and Alzheimer’s disease and related diseases (ADRD), and therefore need to be considered a treatable target (Roseborough A, Hachinski V, Whitehead S. White matter degeneration - a treatable target? Roseborough et al. JAMA Neurol [Internet]. 2020 Apr 27;77(7):793–4, [1]. To help address this often-missed area of research, several workshops have been sponsored by the Leo and Anne Albert Charitable Trust since 2015, resulting in the incorporation of “The Albert Research Institute for White Matter and Cognition” in 2020. The first annual “Institute” meeting was held virtually on March 3–4, 2021. The Institute provides a forum and workspace for communication and support of the advancement of white matter science and research to better understand the evolution and prevention of dementia. It serves as a platform for young investigator development, to introduce new data and debate biology mechanisms and new ideas, and to encourage and support new research collaborations and directions to clarify how white matter changes, with other genetic and health risk factors, contribute to cognitive impairment. Similar to previous Albert Trust–sponsored workshops (Barone et al. in J Transl Med 14:1–14, [2]; Sorond et al. in GeroScience 42:81–96, [3]), established expert investigators were identified and invited to present. Opportunities to attend and present were also extended by invitation to talented research fellows and younger scientists. Also, updates on institute-funded research collaborations were provided and discussed. The summary that follows is a synopsis of topics and discussion covered in the workshop

Transient Nature of Long-Term Nonprogression and Broad Virus-Specific Proliferative T-Cell Responses with Sustained Thymic Output in HIV-1 Controllers

HIV-1(+) individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+) T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+) individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+) patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory