Transaminase-Catalyzed Synthesis of β-Branched Noncanonical Amino Acids Driven by a Lysine Amine Donor.

Transaminases are choice biocatalysts for the synthesis of chiral primary amines, including amino acids bearing contiguous stereocenters. In this study, we employ lysine as a "smart" amine donor in transaminase-catalyzed dynamic kinetic resolution reactions to access β-branched noncanonical arylalanines. Our mechanistic investigation demonstrates that, upon transamination, the lysine-derived ketone byproduct readily cyclizes to a six-membered imine, driving the equilibrium in the desired direction and thus alleviating the need to load superstoichiometric quantities of the amine donor or deploy a multienzyme cascade.

Engineering Hydroxylase Activity, Selectivity, and Stability for a Scalable Concise Synthesis of a Key Intermediate to Belzutifan.

Biocatalytic oxidations are an emerging technology for selective C-H bond activation. While promising for a range of selective oxidations, practical use of enzymes catalyzing aerobic hydroxylation is presently limited by their substrate scope and stability under industrially relevant conditions. Here, we report the engineering and practical application of a non-heme iron and α-ketoglutarate-dependent dioxygenase for the direct stereo- and regio-selective hydroxylation of a non-native fluoroindanone en route to the oncology treatment belzutifan, replacing a five-step chemical synthesis with a direct enantioselective hydroxylation.

Complex drivers of invasive macroalgae boom and bust in Kāne'ohe Bay, Hawai'i.

Invasive macroalgae Eucheuma sp. and Kappaphycus spp. (E/K) became a dominant benthic feature in Kāne'ohe Bay throughout the past four decades - occurring on up to 74 ha of reef area and growing up to three meters thick, which prompted intensive management action.

Public Librarian Perceptions of Assisting Immigrant Patrons: Results from a Multi-State Survey.

Public libraries in the United States (U.S.) are important sources of health information.

Slower Peak Pupillary Response to Emotional Faces in Parents of Autistic Individuals.

Background: Atypical autonomic arousal has been consistently documented in autism spectrum disorder (ASD) and is thought to contribute to the social-communication phenotype of ASD. Some evidence suggests that clinically unaffected first-degree relatives of autistic individuals may also show subtle differences in indices of autonomic arousal, potentially implicating heritable pathophysiological mechanisms in ASD. This study examined pupillary responses in parents of autistic individuals to investigate evidence that atypical autonomic arousal might constitute a subclinical physiological marker of ASD heritability within families of autistic individuals.

Repair of Subacute Intrasubstance Rupture of the Biceps Brachii in a 16-Year-Old Patient.

A 16-year-old boy sustained a complete, closed, intrasubstance rupture of both heads of the biceps brachii after a rope swing accident. The patient was managed with open direct repair of the muscle belly. After the surgery, he underwent an extensive physical therapy regimen and regained full range of motion and strength.

Coral taxonomy and local stressors drive bleaching prevalence across the Hawaiian Archipelago in 2019.

The Hawaiian Archipelago experienced a moderate bleaching event in 2019-the third major bleaching event over a 6-year period to impact the islands. In response, the Hawai'i Coral Bleaching Collaborative (HCBC) conducted 2,177 coral bleaching surveys across the Hawaiian Archipelago. The HCBC was established to coordinate bleaching monitoring efforts across the state between academic institutions, non-governmental organizations, and governmental agencies to facilitate data sharing and provide management recommendations.

[Formula: see text] A cross-cultural study of visual attention in autism spectrum disorder.

Differences in visual attention have been documented in ASD, and appear linked to clinical symptoms. However, most research has been conducted in Western cultures. Because striking differences in visual attention patterns have been documented in other cultures, it is important to understand how culture may influence attentional patterns in ASD.

Neural Processing of Speech Sounds in ASD and First-Degree Relatives.

Efficient neural encoding of sound plays a critical role in speech and language, and when impaired, may have reverberating effects on communication skills. This study investigated disruptions to neural processing of temporal and spectral properties of speech in individuals with ASD and their parents and found evidence of inefficient temporal encoding of speech sounds in both groups. The ASD group further demonstrated less robust neural representation of spectral properties of speech sounds.

A constellation of eye-tracking measures reveals social attention differences in ASD and the broad autism phenotype.

Background: Social attention differences, expressed through gaze patterns, have been documented in autism spectrum disorder (ASD), with subtle differences also reported among first-degree relatives, suggesting a shared genetic link. Findings have mostly been derived from standard eye-tracking methods (total fixation count or total fixation duration). Given the dynamics of visual attention, these standard methods may obscure subtle, yet core, differences in visual attention mechanisms, particularly those presenting sub-clinically.

Holistic analytical characterization and risk assessment of residual host cell protein impurities in an active pharmaceutical ingredient synthesized by biocatalysts.

Host cell proteins (HCPs) are a significant class of process-related impurities commonly associated with the manufacturing of biopharmaceuticals. However, due to the increased use of crude enzymes as biocatalysts for modern organic synthesis, HCPs can also be introduced as a new class of impurities in chemical drugs. In both cases, residual HCPs need to be adequately controlled to ensure product purity, quality, and patient safety.

Retrospective audit of midazolam dose and intravenous sedation record keeping in a primary care oral surgery service.

Regular and robust audit of conscious sedation practice is key to the delivery of safe and effective patient care in all clinical settings. Analysis of outcomes will help to highlight any necessary modifications to procedures and techniques. The Intercollegiate Advisory Committee for Sedation in Dentistry (IACSD) states that conscious sedation procedures must be the subject of robust and regular audit in which every member within the team takes part.

Diverse Catalytic Reactions for the Stereoselective Synthesis of Cyclic Dinucleotide MK-1454.

As practitioners of organic chemistry strive to deliver efficient syntheses of the most complex natural products and drug candidates, further innovations in synthetic strategies are required to facilitate their efficient construction. These aspirational breakthroughs often go hand-in-hand with considerable reductions in cost and environmental impact. Enzyme-catalyzed reactions have become an impressive and necessary tool that offers benefits such as increased selectivity and waste limitation.

A kinase-cGAS cascade to synthesize a therapeutic STING activator.

The introduction of molecular complexity in an atom- and step-efficient manner remains an outstanding goal in modern synthetic chemistry. Artificial biosynthetic pathways are uniquely able to address this challenge by using enzymes to carry out multiple synthetic steps simultaneously or in a one-pot sequence. Conducting biosynthesis ex vivo further broadens its applicability by avoiding cross-talk with cellular metabolism and enabling the redesign of key biosynthetic pathways through the use of non-natural cofactors and synthetic reagents.

Childhood Academic Performance: A Potential Marker of Genetic Liability to Autism.

Autism spectrum disorder (ASD), a heritable neurodevelopmental disorder, confers genetic liability that is often expressed among relatives through subclinical, genetically-meaningful traits, or endophenotypes. For instance, relative to controls, parents of individuals with ASD differ in language-related skills, with differences emerging in childhood. To examine ASD-related endophenotypes, this study investigated developmental academic profiles among clinically unaffected siblings of individuals with ASD (n = 29).

The genomic basis of army ant chemosensory adaptations.

The evolution of mass raiding has allowed army ants to become dominant arthropod predators in the tropics. Although a century of research has led to many discoveries about behavioural, morphological and physiological adaptations in army ants, almost nothing is known about the molecular basis of army ant biology. Here we report the genome of the iconic New World army ant Eciton burchellii, and show that it is unusually compact, with a reduced gene complement relative to other ants.

The Phenotypic Profile Associated With the Premutation in Women: An Investigation of Clinical-Behavioral, Social-Cognitive, and Executive Abilities.

The gene in its premutation (PM) state has been linked to a range of clinical and subclinical phenotypes among PM carriers, including some subclinical traits associated with autism spectrum disorder (ASD). This study attempted to further characterize the phenotypic profile associated with the PM by studying a battery of assessments examining clinical-behavioral traits, social-cognitive, and executive abilities in women carrying the PM, and associations with -related variability. Participants included 152 female PM carriers and 75 female controls who were similar in age and IQ, and screened for neuromotor impairments or signs of fragile X-associated tremor/ataxia syndrome.

The perspectives of people who use drugs regarding short term involuntary substance use care for severe substance use disorders.

Background: In the Canadian Province of British Columbia (BC), the BC Mental Health Act permits involuntary care for treating mental disorders. However, the Act has also been applied to provide involuntary care to individuals with a primary substance use disorder, in the absence of specific guidelines and legislation, and with insufficient understanding of perspectives of people who use drugs (PWUD) regarding this approach.

Methods: As part of a larger mixed-methods research project providing an overview of involuntary care for severe substance use disorders in BC, three focus groups were convened with: PWUD, families and caregivers, and Indigenous community stakeholders.

How Public Libraries Help Immigrants Adjust to Life in a New Country: A Review of the Literature.

Public library programs and services offer opportunities to help immigrants navigate daily life in unfamiliar surroundings and a new language. For example, language classes address the social determinants of health as they encourage social participation and community ties and help develop friendships. The purpose of this research was to conduct a narrative literature review to understand how immigrants use public libraries and how public library services influence the social determinants of health for immigrant populations.

A Unique Visual Attention Profile Associated With the Premutation.

Atypical visual attention patterns have been observed among carriers of the fragile X mental retardation gene () premutation (PM), with some similarities to visual attention patterns observed in autism spectrum disorder (ASD) and among clinically unaffected relatives of individuals with ASD. Patterns of visual attention could constitute biomarkers that can help to inform the neurocognitive profile of the PM, and that potentially span diagnostic boundaries. This study examined patterns of eye movement across an array of fixation measurements from three distinct eye-tracking tasks in order to investigate potentially overlapping profiles of visual attention among PM carriers, ASD parents, and parent controls.

A Cadaveric Study on the Utility of the Levator Scapulae Motor Nerve as a Donor for Brachial Plexus Reconstruction.

Purpose: The purpose of the study was to evaluate the utility of the levator scapulae motor nerve (LSN) as a donor nerve for brachial plexus nerve transfer. We hypothesized that the LSN could be transferred to the suprascapular nerve (SSN) or long thoracic nerve (LTN) with a reliable tension-free coaptation and appropriate donor-to-recipient axon count ratio.

Methods: Twelve brachial plexus dissections were performed on 6 adult cadavers, bilaterally.

Lymphatic filariasis in Fiji: progress towards elimination, 1997-2007.

Background: Lymphatic filariasis (LF) is a major public health problem in the Pacific Region, including in Fiji. Through transmission by the mosquito vector , Fiji has suffered the burden of remaining endemic with LF despite efforts at elimination prior to 1999. In the year 1999, Fiji agreed to take part in the Pacific Programme for Elimination of LF (PacELF) and the Global Programme to Eliminate LF.

Association of Perioperative Computed Tomography Hounsfield Units and Failure of Femoral Neck Fracture Fixation.

Objectives: To determine whether Hounsfield units (HUs) measured on perioperative computed tomographic scans are associated with radiographic outcomes and reoperations after femoral neck fracture fixation.

Design: Retrospective cohort study.

Setting: Level I trauma center.