Increasing radial growth in old-growth high-elevation conifers in Southern California, USA, during the exceptional "hot drought" of 2000-2020.

Hot droughts, droughts attributed to below-average precipitation and exceptional warmth, are increasingly common in the twenty-first century, yet little is known about their effect on coniferous tree growth because of their historical rarity. In much of the American West, including California, radial tree growth is principally driven by precipitation, and narrow ring widths are typically associated with either drier or drought conditions. However, for species growing at high elevations (e.g., Larix lyalli, Pinus albicaulis), growth can be closely aligned with above-average temperatures with maximum growth coinciding with meteorological drought, suggesting that the growth effects of drought span from adverse to beneficial depending on location. Here, we compare radial growth responses of three high-elevation old-growth pines (Pinus jeffreyi, P. lambertiana, and P. contorta) growing in the San Jacinto Mountains, California, during a twenty-first-century hot drought (2000-2020) largely caused by exceptional warmth and a twentieth-century drought (1959-1966) principally driven by precipitation deficits. Mean radial growth during the hot drought was 12% above average while 18% below average during the mid-century drought illustrating that the consequences of environmental stress exhibit spatiotemporal variability. We conclude that the effects of hot droughts on tree growth in high-elevation forests may produce responses different than what is commonly associated with extended dry periods for much of western North America's forested lands at lower elevational ranges and likely applies to other mountainous regions (e.g., Mediterranean Europe) defined by summer-dry conditions. Thus, the climatological/biological interactions discovered in Southern California may offer clues to the unique nature of high-elevation forested ecosystems globally.

Third-Generation Anticancer Photodynamic Therapy Systems Based on Star-like Anionic Polyacrylamide Polymer, Gold Nanoparticles, and Temoporfin Photosensitizer.

Photodynamic therapy (PDT) is a non-invasive anticancer treatment that uses special photosensitizer molecules (PS) to generate singlet oxygen and other reactive oxygen species (ROS) in a tissue under excitation with red or infrared light. Though the method has been known for decades, it has become more popular recently with the development of new efficient organic dyes and LED light sources. Here we introduce a ternary nanocomposite: water-soluble star-like polymer/gold nanoparticles (AuNP)/temoporfin PS, which can be considered as a third-generation PDT system. AuNPs were synthesized in situ inside the polymer molecules, and the latter were then loaded with PS molecules in an aqueous solution. The applied method of synthesis allows precise control of the size and architecture of polymer nanoparticles as well as the concentration of the components. Dynamic light scattering confirmed the formation of isolated particles (120 nm diameter) with AuNPs and PS molecules incorporated inside the polymer shell. Absorption and photoluminescence spectroscopies revealed optimal concentrations of the components that can simultaneously reduce the side effects of dark toxicity and enhance singlet oxygen generation to increase cancer cell mortality. Here, we report on the optical properties of the system and detailed mechanisms of the observed enhancement of the phototherapeutic effect. Combinations of organic dyes with gold nanoparticles allow significant enhancement of the effect of ROS generation due to surface plasmonic resonance in the latter, while the application of a biocompatible star-like polymer vehicle with a dextran core and anionic polyacrylamide arms allows better local integration of the components and targeted delivery of the PS molecules to cancer cells. In this study, we demonstrate, as proof of concept, a successful application of the developed PDT system for in vitro treatment of triple-negative breast cancer cells under irradiation with a low-power LED lamp (660 nm). We consider the developed nanocomposite to be a promising PDT system for application to other types of cancer.

Health impacts of poor water quality on an endangered shorebird breeding programme in Aotearoa New Zealand.

CASE HISTORY: Two clusters of mortality among endangered tuturuatu/tchuriwat'/shore plover (Thinornis novaeseelandiae) have occurred at captive breeding facilities around New Zealand in recent years. In the first, four chicks died at Pukaha National Wildlife Centre (Mount Bruce, NZ) in February 2016, and in the second five adult birds at the Cape Sanctuary (Cape Kidnappers, NZ) died in 2022. CLINICAL FINDINGS: In 2016, four chicks were noted to become weak, have increased vocalisations and closed eyes prior to death. The remaining chicks were treated for 5 days with amoxycillin/clavulanate orally twice daily. Water containers and brooders were cleaned and disinfected with chlorhexidine. No further mortality was seen.In the 2022 cluster, three adult breeding birds died acutely and five others showed inappetence, weight loss and diarrhoea approximately 10 days after heavy rains flooded the local river. The five birds were treated with amoxycillin/clavulanate orally twice daily and oral fluids for 5 days. Two birds died and three survived. No breeding occurred in the aviaries in the following season. PATHOLOGICAL FINDINGS: In 2016, the chicks showed pulmonary changes ranging from congestion and oedema to heterophilic inflammation consistent with septicaemia.In 2022, the adult birds showed proliferation of bacteria in the distal small intestine associated with mucosal ulceration and heterophilic infiltration. Acid-fast staining of the caecal contents in one bird showed organisms consistent with Cryptosporidium spp. LABORATORY FINDINGS: Aerobic bacterial cultures of the lung and liver of two affected chicks carried out in 2016 showed heavy growth of Plesiomonas shigelloides. The same organism was cultured from water trays and holding tanks containing water boatmen (Sigara arguta) on which the chicks were fed.In 2022, cultures from the livers of three dead birds each showed a mixed bacterial growth with differing dominant organisms (Aeromonas sobria, Hafnia alvei, Citrobacter freundii and an Enterococcus sp.). PCR and sequencing confirmed Cryptosporidium parvum in the caecum of one bird. Fresh faeces from 24 breeding birds from the captive breeding facilities were negative by PCR for Cryptosporidium spp.The captive breeding facilities obtain water for the aviaries and aquatic invertebrates to feed to the chicks from local freshwater sources. Water quality testing at the Cape Sanctuary revealed concentrations of faecal indicator bacteria in excess of safe drinking water guidelines, with peaks following heavy rainfall. CLINICAL RELEVANCE: Fluctuations in water quality associated with mammalian faecal bacteria can adversely affect bird health and impact on captive rearing of endangered wildlife.

Musculoskeletal injuries during trail sports: Sex- and age-specific analyses over 20 years from a national injury database.

INTRODUCTION: Musculoskeletal (MSK) injuries in US trail sports are understudied as trail sport popularity grows. This study describes MSK injury patterns among hikers, trail runners, and mountain bikers from 2002 through 2021 and investigates MSK injury trends acquired during mountain sports. METHODS: The National Electronic Injury Surveillance System (NEISS) was used to identify US emergency department (ED) patients from 2002-2021 (inclusive) who endured MSK injuries during hiking, trail running, or mountain biking. Injury rates and national estimates were calculated across demographics. RESULTS: 9835 injuries were included (48.4% male, 51.6% female). Injuries increased over time, with 1213 from 2002-2005 versus 2417 from 2018-2021. No sex differences existed before 2010, after which female injury rates exceeded those of males. The following findings were statistically significant, with P<0.05: females endured more fractures and strains/sprains; males endured more lacerations; concussions and head injuries were higher among those <18 y; dislocations and strains/sprains were higher for 18 to 65 y; fractures were higher for >65 y; <18 y had high mountain-biking and low running rates; 18 to 65 y had high running rates; and >65 y had low biking and running rates. Although all diagnoses increased in number over time, no significant differences existed in the proportion of any given diagnosis relative to total injuries. CONCLUSIONS: MSK injuries during trail sports have increased since 2002. Males endured more injuries until 2009, after which females endured more. Significant sex and age differences were found regarding injury diagnosis and body parts. Further studies are needed to confirm these trends and their causes.

Palladium-Catalyzed Carbonylations: Application in Complex Natural Product Total Synthesis and Recent Developments.

Carbon monoxide is a cheap and abundant C1 building block that can be readily incorporated into organic molecules to rapidly build structural complexity. In this Perspective, we outline several recent (since 2015) examples of palladium-catalyzed carbonylations in streamlining complex natural product total synthesis and highlight the strategic importance of these carbonylation reactions in the corresponding synthesis. The selected examples include spinosyn A, callyspongiolide, perseanol, schizozygane alkaloids, cephanolides, and bisdehydroneostemoninine and related stemona alkaloids. We also provide our perspective about the recent advancements and future developments of palladium-catalyzed carbonylations.

Aging of Copper Nanoparticles in the Marine Environment Regulates Toxicity for a Coastal Phytoplankton Species.

Environmental conditions in aquatic ecosystems transform toxic chemicals over time, influencing their bioavailability and toxicity. Using an environmentally relevant methodology, we tested how exposure to seawater for 1-15 weeks influenced the accumulation and toxicity of copper nanoparticles (nano-Cu) in a marine phytoplankton species. Nano-Cu rapidly agglomerated in seawater and then decreased in size due to Cu dissolution. Dissolution rates declined during weeks 1-4 and remained low until 15 weeks, when the large agglomerates that had formed began to rapidly dissolve again. Marine phytoplankton species were exposed for 5-day periods to nano-Cu aged from 1 to 15 weeks at concentrations from 0.01 to 20 ppm. Toxicity to phytoplankton, measured as change in population growth rate, decreased significantly with particle aging from 0 to 4 weeks but increased substantially in the 15-week treatment due apparently to elevated Cu dissolution of reagglomerated particles. Results indicate that the transformation, fate, and toxicity of nano-Cu in marine ecosystems are influenced by a highly dynamic physicochemical aging process.

Chronic calcific tendonitis of the rotator cuff: a systematic review and meta-analysis of randomized controlled trials comparing operative and nonoperative interventions.

BACKGROUND: Calcific tendinitis is a relatively common shoulder disorder, with 7%-17% of individuals with shoulder pain having rotator cuff calcium deposits. Several nonoperative interventions, extracorporeal shockwave therapy (ESWT) and ultrasonography-guided needling (UGN), and surgical techniques have been described to treat calcific tendonitis with satisfactory outcomes. Clinical guidelines are lacking for surgical excision in cases refractory to nonoperative treatment. Several arthroscopic and open operative techniques have been described to treat calcific tendonitis with satisfactory clinical outcomes. The purpose of this systematic review of randomized controlled trials is to compare outcomes and complications of nonoperative vs. operative management of chronic calcific tendinitis of the rotator cuff, to provide evidence-based treatment guidelines for practitioners. METHODS: EMBASE, PubMed, and OVID [MEDLINE] were searched from database inception until February 20, 2022, for randomized controlled trials reporting outcomes related to operative or nonoperative management for calcific tendonitis of the shoulder. Clinical outcomes including pain on visual analog scale (VAS), Constant-Murley Shoulder Outcome Score (CMS), and resolution of calcific deposits were evaluated. Continuous data at last follow-up was pooled into mean differences using a random effects model for meta-analysis. RESULTS: A total of 27 studies (2212 nonoperative patients and 140 operative patients) met the final inclusion criteria. Pooled mean difference in VAS for ESWT was -3.83 (95% confidence interval [CI] -5.38, -2.27); P < .001), compared to -4.83 (95% CI -5.44, -4.22; P < .001) for UGN, and -4.65 (95% CI -5.47, -3.82; P < .001) for the operative interventions. Pooled mean difference in CMS score after ESWT was 18.30 (95% CI 10.95, 25.66; P < .001) compared to 22.01 (95% CI 8.17, 35.84; P = .002) for UGN, and 38.35 (95% CI 31.68, 45.02; P < .001) for the operative interventions. Eighty-five percent of patients receiving operative and 67% of patients receiving UGN management had complete radiographic resolution of calcific deposit. CONCLUSIONS: Surgical treatment of chronic calcific tendonitis of the rotator cuff results in larger improvement in functional outcome scores and comparable pain reduction to nonoperative interventions, particularly UGN. Both operative and nonoperative treatment modalities are likely to have clinically significant improvements in function and pain, and thus it is reasonable to trial UGN and ESWT as first-line treatment. Cost-effectiveness analyses will be needed to support one treatment over the other. High-quality randomized controlled trials directly comparing nonoperative interventions to operative interventions in patients prior to failing conservative treatment are needed to establish high-quality evidence-based guidelines.

Seven-Week Accommodating Resistance Training Improves Wingate Peak Power But Not Muscular Strength or Endurance in Strength-Trained Females.

ABSTRACT: Parten, AL, Barker, GA, O'Neal, EK, and Waldman, HS. Seven-week accommodating resistance training improves Wingate peak power but not muscular strength or endurance in strength-trained females. J Strength Cond Res 37(9): 1789-1794, 2023-Accommodating resistance (AR) is a training technique that includes attaching elastic bands or chains to a loaded barbell to alter the resistance profile throughout the barbell movement. This study was the first to quantify the effects of AR versus a traditional resistance (TR) training program on changes in strength and power profiles in a trained female cohort. Resistance-trained (training history: 2.4 ± 1.4 years) females (age: 22.1 ± 3.0 years) completed baseline and postintervention tasks which included 1 repetition maximum (1RM) testing in the back squat (BS) and bench press (BP), a repetitions to failure in the BP (60% of 1RM), and 1 30-s Wingate test. After baseline testing, subjects were stratified (based on relative strength) into either the AR ( n = 9) or TR ( n = 10) group and then completed a supervised, 7-week training intervention. Both groups improved their 1RM in both lifts, but no statistical differences were found between groups in 1RM for BS, BP, or BP to failure ( p > 0.05). However, the AR group increased Wingate peak power (837 ± 221 to 901 ± 215 W; p = 0.04), whereas TR (868 ± 244 to 8,343 ± 182 W; p = 0.47) did not. This study supports AR with lighter relative barbell load incurs similar strength adaptations as TR. For coaches training athletes concerned with power, AR may be advantageous for improving rate of force development as demonstrated by large increases in peak Wingate power.

Astaxanthin Supplementation Does Not Affect Markers of Muscle Damage or Inflammation After an Exercise-Induced Muscle Damage Protocol in Resistance-Trained Males.

ABSTRACT: Waldman, HS, Bryant, AR, Parten, AL, Grozier, CD, and McAllister, MJ. Astaxanthin supplementation does not affect markers of muscle damage or inflammation after an exercise-induced muscle damage protocol in resistance-trained males. J Strength Cond Res 37(7): e413-e421, 2023-It is well documented that exercise-induced muscle damage (EIMD) decreases exercise performance by elevated inflammation and subjective discomfort. Due to its potent antioxidative properties, astaxanthin (AX) may serve as a potential dietary supplement strategy for mitigating delayed-onset muscle soreness (DOMS) and enhancing recovery and performance. This study aimed to investigate the effects of AX on markers of muscle damage, inflammation, DOMS, and anaerobic performance and substrate metabolism. Thirteen resistance-trained men (mean ± SD , age, 23.4 ± 2.1 years) completed a double-blind, counterbalanced, and crossover design with a 1-week washout period between 2, 4-week supplementation periods at 12 mg·d -1 of AX or placebo. After each supplementation period, subjects completed 2 trials, with trial 1 including a graded exercise test (GXT) and a 30-second Wingate and trial 2 including an EIMD protocol followed by the collection of fasting blood samples (pre-post) to measure creatine kinase, advanced oxidative protein products, C-reactive protein, interleukin-6, insulin, and cortisol. Astaxanthin supplementation had no statistical effects on markers of substrate metabolism during the GXT, Wingate variables, or markers of muscle damage, inflammation, or DOMS when compared with placebo (all p > 0.05). However, 4 weeks of AX supplementation did significantly lower oxygen consumption during the final stage of the GXT (12%, p = 0.02), as well as lowered systolic blood pressure (∼7%, p = 0.04), and significantly lowered baseline insulin values (∼24%, p = 0.05) when compared with placebo. Collectively, these data suggest that 4 weeks of AX supplementation at 12 mg·d -1 did not affect markers of muscle damage, inflammation, or DOMS after an EIMD protocol in a resistance-trained male cohort.

Assessment of Metabolic Flexibility by Substrate Oxidation Responses and Blood Lactate in Women Expressing Varying Levels of Aerobic Fitness and Body Fat.

ABSTRACT: Waldman, HS, Bryant, AR, Knight, SN, Killen, LG, Davis, BA, Robinson, MA, and O'Neal, EK. Assessment of metabolic flexibility by substrate oxidation responses and blood lactate in women expressing varying levels of aerobic fitness and body fat. J Strength Cond Res 37(3): 581-588, 2023-Collection of substrate oxidation responses during exercise is proposed as a noninvasive means for assessing metabolic flexibility in male subjects. However, because of hormonal and metabolic differences between sexes, this method may not be applicable to female subjects. This study assessed metabolic flexibility through indirect calorimetry across female subjects with different maximal oxidative capacities. Thirty-eight (18-45 years) eumenorrheic female subjects were stratified ( p < 0.05) based on V̇ o2 peak (mL·kg -1 ·min -1 ) into (1) endurance-trained (ET, n = 12, 42.6 ± 5.3), (2) recreationally active (RA, n = 13, 32.3 ± 1.6), or (3) overweight female subjects (OW, n = 13, 21.0 ± 4.0). Subjects completed the same 5-stage graded exercise test with intensities of 30, 45, 60, 75, and 90 W. Lactate [La - ], carbohydrate (CHOox), and fat (FATox) oxidation rates were assessed during the last min of each 5-minute stage. Subjects then cycled to exhaustion to determine V̇ o2 peak. Endurance-trained and RA female subjects expressed significantly ( p ≤ 0.05) higher absolute rates and rates scaled to fat-free mass of CHOox and FATox compared with OW female subjects during multiple stages. [La - ] failed to consistently differentiate the 3 groups with higher [La - ] for OW only found during stage 4; however, RER differed by 0.09 units or more at each stage for OW vs. ET. It seems that RER was more sensitive to cohort characteristics than [La - ] contrasting recent findings in male cohorts. In conclusion, indirect calorimetry is a practical and noninvasive method for assessing metabolic flexibility in eumenorrheic female subjects of varying aerobic fitness levels.

A Self-Selected 16:8 Time-Restricted Eating Protocol Improves Fat Oxidation Rates, Markers of Cardiometabolic Health, and 10-km Cycling Performance in Middle-Age Male Cyclists.

ABSTRACT: Witt, CR, Grozier, CD, Killen, LG, Renfroe, LG, O'Neal, EK, and Waldman, HS. A self-selected 16:8 time-restricted eating protocol improves fat oxidation rates, markers of cardiometabolic health, and 10-km cycling performance in middle-age male cyclists. J Strength Cond Res 37(5): 1117-1123, 2023-The purpose of this study was to assess the impact of 4 weeks, 16:8 time restricted eating (TRE) on markers of metabolic health and 10-km time trial (TT) performance in middle-age male cyclists. Subjects ( n = 12; age, 40-60 years; V̇ o2 peak, 41.8 ± 5.6 ml·kg -1 ·min -1 ) consisting of individuals following a habitual Western diet completed a familiarization and 2 experimental trials [PRE] and [POST]. Following habitual Western diet without TRE, anthropometric measures were assessed, followed by completion of a graded exercise test and 10-km TT. Subjects then adhered to a 4-week TRE protocol where all calories had to be consumed within a self-selected 8-hour window and then returned for repeat testing. Although self-reported caloric intake did not statistically change PRE to POST, body mass (PRE, 83.2 ± 13.4 vs. POST, 80.7 ± 12.6 kg), fat mass (∼2.5 kg), and blood pressure (systolic, 8 mm Hg; diastolic, 4 mm Hg) were all significantly lower POST (all p < 0.05), with no changes in fat-free mass. Furthermore, fat oxidation significantly increased (PRE, 0.36 ± 0.03 vs. POST, 0.42 ± 0.03 g·min -1 ; p = 0.04) following the TRE intervention and 10-km TT performance improved by ∼2 minutes POST (PRE, 29.7 ± 7.3 vs. POST, 27.4 ± 5.5 minutes; p = 0.02). Overall, our data demonstrated that middle-age male cyclists adhering to a 4-week TRE protocol can improve their body composition profile and 10-km TT performance without detriments to fat-free mass.

Cardiac morphology of North Island brown kiwi (Apteryx mantelli).

AIMS: To investigate the cardiac anatomy of North Island brown kiwi (Apteryx mantelli) through heart morphometric parameters measured at post-mortem examination. METHODS: Morphometric cardiac parameters were established at post-mortem examination of 20 North Island brown kiwi. Birds were classified by gender and age (chicks vs. adults). Measurements included: body mass, heart mass, sternal length, midpoint thickness of left ventricular free wall, midpoint thickness of right ventricular free wall and ratios of heart mass to body mass, left ventricular length to sternal length, right ventricular length to sternal length, length of left ventricle to right ventricle, interventricular septal thickness relative to the sternal length and interventricular septal thickness relative to the left ventricular length. Unadjusted estimates of the median difference and their 95% CI were then reported at each age and sex for all the cardiac morphometric parameters and their ratios. RESULTS: The small sample size led to wide 95% CI for the median difference between gender and age for the cardiac morphometric measurements. Nevertheless, between adult female and male kiwi, the estimated population median differences for heart mass (2.2 (95% CI = -2.9-5.6) g), length (1.2 (95% CI = -2.2-5.6) mm), width (6.1 (95% CI = -1.0-8.2) mm), left ventricular free wall length (5.5 (95% CI = -0.5-8.8) mm) and right ventricular free wall length (2.6 (95% CI = -3.7-6.9) mm) were established. In adult North Island brown kiwi, the heart mass is 0.8 (95% CI = 0.7-0.8)% of the body mass. CONCLUSIONS: The precision of the differences noted in heart measurements recorded between male and female kiwi at each age was limited by the low sample size available for this study. This led to wide CI and an inability to adjust differences observed for gender by differences in other confounders such as body size. With this caveat, there is weak evidence that adult female kiwi have a larger heart size and mass than the adult males. CLINICAL RELEVANCE: These results can be used to improve the diagnosis of cardiac disease in kiwi at post-mortem examination and aid in interpretation of the results of echocardiography in live birds for the antemortem diagnosis of cardiac disorders.

Causes of mortality of kiwi (Apteryx spp.) in New Zealand: a retrospective analysis of post-mortem records, 2010-2020.

AIMS: To examine and assess causes of mortality of kiwi (Apteryx spp.) submitted to Massey University between 2010 and 2020 across the five recognised species according to location, age group and captivity status in New Zealand. METHODS: Post-mortem reports were obtained from the Massey University/Te Kunenga ki Purehuroa School of Veterinary Science/Wildbase Pathology Register. Inclusion criteria were all species of kiwi with a date of post-mortem examination between August 2010 and August 2020. Data from each report was exported, categorised and compared using Microsoft Excel. RESULTS: Of a total of 1,005 post-mortem reports, there were 766 North Island brown kiwi (NIBK; A. mantelli), 83 tokoeka (A. australis), 73 rowi (A. rowi), 49 great spotted kiwi (A. haastii), and 34 little spotted kiwi (A. owenii). This comprised 19 eggs/embryos, 125 neonatal, 473 juvenile, 153 subadult, and 235 adult kiwi. There were 615 kiwi from wild populations, 148 from sanctuary populations, 238 from captivity, and four from unspecified locations. The leading cause of death was trauma, affecting 322 (32.0 (95% CI = 29.2-35.0)%) kiwi including 289 (37.3 (95% CI = 26.0-31.7)%) NIBK. Nearly half of these died from predation by mustelids, with losses recorded from neonates to adults and clustered in the central to southern North Island. Predation by dogs was the second most common cause of death, killing 84 (8.4 (95% CI = 6.7-10.2)%) kiwi, of which 65.5% came from the northern districts of the North Island. Non-infectious disease killed 214 (21 (95% CI = 18.8-24.0)%) kiwi, and included developmental deformities, gastrointestinal foreign bodies and predator trap injuries. Infectious disease killed 181 (18.0 (95% CI = 15.7-20.5)%) kiwi and the proportion decreased with age, with common diagnoses including coccidiosis, bacterial septicaemia, avian malaria, and fungal respiratory disease. Starvation affected 42 (4.2 (95% CI = 3.0-5.6)%) kiwi, comprised of mainly neonatal or juvenile individuals from wild or sanctuary populations, with a higher percentage seen in tokoeka (11/83; 13.3%) compared to other species (min 0%, max 5.9%). The cause of death was undetermined in 246 (24.5 (95% CI = 21.8-27.3)%) cases, which was most often due to poor preservation of remains. This included 33/73 (46%) rowi and 32/83 (39%) tokoeka, and affected mainly birds from sanctuary and wild populations. CONCLUSIONS: This study enhances our understanding of causes of mortality in captive, wild and sanctuary populations of all kiwi species and age groups within contemporary New Zealand.

A lower motor neuron disease in takahe (Porphyrio hochstetteri) is an endoplasmic reticulum storage disease.

AIMS: To investigate the pathogenesis of a disease in takahe (Porphyrio hochstetteri) with intracytoplasmic inclusion bodies in lower motor neurons. METHODS: Four birds aged between 5 and 12 years, from three different wildlife sanctuaries in New Zealand were examined. Of these, only one had signs of spinal dysfunction in the form of paresis. Stained paraffin sections of tissues were examined by light microscopy and immunostained sections of the ventral horn of the spinal cord by confocal microscopy. Epoxy resin sections of the spinal cord from the bird with spinal dysfunction were examined by electron microscopy. RESULTS: Two types of inclusion bodies were noted, but only in motor neurons of the ventral spinal cord and brain stem. These were large globoid eosinophilic bodies up to 5 µm in diameter, and yellow/brown granular inclusions mostly at the pole of the cell. The globoid bodies stained with Luxol fast blue but not with periodic acid Schiff (PAS), or Sudan black. The granular inclusions stained with Luxol fast blue, PAS and Sudan black. Both bodies were slightly autofluorescent. On electron microscopy the globoid bodies had an even electron-dense texture and were bound by a membrane. Beneath the membrane were large numbers of small intraluminal vesicles. The smaller granular bodies were more heterogeneous, irregularly rounded and membrane-bound accumulations of granular electron-dense material, often with electron-lucent vacuoles. Others were more vesicular but contained varying amounts of electron-dense material. The large globoid bodies did not immunostain for lysosomal markers lysosomal associated protein 1 (LAMP1) or cathepsin D, so were not lysosomal. The small granular bodies stained for cathepsin D by a chromogenic method.A kindred matrix analysis showed two cases to be as closely related as first cousins, and another case was almost as closely related to one of them, but the fourth bird was unrelated to any other. CONCLUSIONS: It was concluded that this was an endoplasmic reticulum storage disease due to a specific protein misfolding within endoplasmic reticulum. It was rationalised that the two types of inclusions reflected the same aetiology, but that misfolded protein in the smaller granular bodies had entered the lysosomal system via endoplasmic reticulum autophagy. Although the cause was unclear, it most likely had a genetic aetiology or predisposition and, as such, has clinical relevance.

Size-dependent mortality of corals during marine heatwave erodes recovery capacity of a coral reef.

For many long-lived taxa, such as trees and corals, older, and larger individuals often have the lowest mortality and highest fecundity. However, climate change-driven disturbances such as droughts and heatwaves may fundamentally alter typical size-dependent patterns of mortality and reproduction in these important foundation taxa. Working in Moorea, French Polynesia, we investigated how a marine heatwave in 2019, one of the most intense marine heatwaves at our sites over the past 30 years, drove patterns of coral bleaching and mortality. The marine heatwave drove island-wide mass coral bleaching that killed up to 76% and 65% of the largest individuals of the two dominant coral genera, Pocillopora and Acropora, respectively. Colonies of Pocillopora and Acropora ≥30 cm diameter were ~3.5× and ~1.3×, respectively, more likely to die than colonies <30-cm diameter. Typically, annual mortality in these corals is concentrated on the smallest size classes. Yet, this heatwave dramatically reshaped this pattern, with heat stress disproportionately killing larger coral colonies and equalizing annual mortality rates across the size spectrum. This shift in the size-mortality relationship reduced the overall fecundity of these genera by >60% because big corals are disproportionately important for reproduction on reefs. Additionally, the survivorship of microscopic coral recruits, critical for the recovery of corals following disturbances, declined to 2%, over an order of magnitude lower compared to a year without elevated thermal stress, where 33% of coral recruits survived. While other research has shown that larger corals can bleach more frequently than smaller corals, we show the severe impact this phenomenon can have at the reef-wide scale. As marine heatwaves become more frequent and intense, disproportionate mortality of the largest, most fecund corals and near-complete loss of entire cohorts of newly-settled coral recruits will likely reduce the recovery capacity of these iconic ecosystems.

Nickel-Catalyzed Tandem Ueno-Stork Cyclization: Stereoselective 1,2-Dicarbofunctionalization of Cyclic Alkenes.

A nickel-catalyzed tandem Ueno-Stork cyclization is developed to enable stereoselective 1,2-dicarbofunctionalization of cyclic alkenes and efficiently build various bicyclic products. This new protocol does not involve any toxic or difficult-to-remove tin reagent and is scalable and amenable to build all-carbon quaternary centers.

Blistering1 Modulates Penicillium expansum Virulence Via Vesicle-mediated Protein Secretion.

The blue mold fungus, Penicillium expansum, is a postharvest apple pathogen that contributes to food waste by rotting fruit and by producing harmful mycotoxins (e.g. patulin). To identify genes controlling pathogen virulence, a random T-DNA insertional library was created from wild-type P. expansum strain R19. One transformant, T625, had reduced virulence in apples, blistered mycelial hyphae, and a T-DNA insertion that abolished transcription of the single copy locus in which it was inserted. The gene, Blistering1, encodes a protein with a DnaJ domain, but otherwise has little homology outside the Aspergillaceae, a family of fungi known for producing antibiotics, mycotoxins, and cheese. Because protein secretion is critical for these processes and for host infection, mass spectrometry was used to monitor proteins secreted into liquid media during fungal growth. T625 failed to secrete a set of enzymes that degrade plant cell walls, along with ones that synthesize the three final biosynthetic steps of patulin. Consequently, the culture broth of T625 had significantly reduced capacity to degrade apple tissue and contained 30 times less patulin. Quantitative mass spectrometry of 3,282 mycelial proteins revealed that T625 had altered cellular networks controlling protein processing in the endoplasmic reticulum, protein export, vesicle-mediated transport, and endocytosis. T625 also had reduced proteins controlling mRNA surveillance and RNA processing. Transmission electron microscopy of hyphal cross sections confirmed that T625 formed abnormally enlarged endosomes or vacuoles. These data reveal that Blistering1 affects internal and external protein processing involving vesicle-mediated transport in a family of fungi with medical, commercial, and agricultural importance.

Impact of Time Restricted Feeding on Markers of Cardiometabolic Health and Oxidative Stress in Resistance-Trained Firefighters.

ABSTRACT: McAllister, MJ, Gonzalez, AE, and Waldman, HS. Impact of time restricted feeding on markers of cardiometabolic health and oxidative stress in resistance-trained firefighters. J Strength Cond Res 36(9): 2515-2522, 2022-Firefighters are often exposed to numerous occupational stressors that cause inflammation, oxidative stress (OS), and elevated risk for developing cardiometabolic disease. Time-restricted feeding (TRF) has been shown to result in favorable changes in markers of inflammation and cardiometabolic health. This study investigated the impact of a 6-week TRF intervention (14:10; fasting:feeding) in resistance-trained firefighters. Blood was analyzed for several markers of inflammation, OS, and cardiometabolic health: insulin, ghrelin, leptin, glucagon, adiponectin, resistin, advanced glycated end products (AGE), advanced oxidation protein products, total nitrite-nitrate levels, tumor necrosis factor-α, interleukin (IL)-6, IL-8, IL-10, as well as glucose and lipid levels. A graded exercise test was also conducted before and after the TRF intervention, and substrate oxidation rates were calculated and compared before and after the intervention. Comparisons pre and post TRF were determined with dependent t -tests. Time-restricted feeding resulted in significant reductions in advanced oxidation protein products (∼31%) and AGEs (∼25%); however, no other changes were found. These findings suggest that TRF may be a nutrition intervention aimed at improving some select markers of cardiometabolic health in firefighters, namely, by the reductions in advanced oxidation protein products and AGEs.

No Effect of a Ketone Monoester on Markers of Stress and Performance in a Live-Burn Search and Rescue in Firefighters.

ABSTRACT: Waldman, HS, Bryant, AR, Shepherd, BD, Egan, B, and McAllister, MJ. No effect of a ketone monoester on markers of stress and performance in a live-burn search and rescue in firefighters. J Strength Cond Res 36(3): 763-771, 2022-Firefighters experience a range of stressors that impair performance and elevate the risk for developing cardiometabolic diseases. ß-Hydroxybutyrate (ßHB) has been shown to mitigate markers of oxidative stress and inflammation and serve as an alternative fuel with implications to physical performance. On 2 occasions in a double-blind, counterbalanced, and crossover design, 14 professional firefighters performed a live-burn, search and rescue (S&R) 30 minutes after ingestion of a ketone monoester (KME; 0.5 g·kg-1) or a placebo (PLA). Dependent variables collected before and after the S&R included salivary markers of stress and inflammation (cortisol, α-amylase, interleukin-1 beta, uric acid), perceptual markers (profile of mood state [POMS]), gastrointestinal distress (GI), rating of perceived exertion [RPE]), time to completion, and capillary blood measurement of ßHB and glucose. KME resulted in capillary ßHB concentrations of approximately 2.1-3.2 mM throughout the protocol. Capillary glucose concentrations were lower for the KME compared with PLA (∼7%) (interaction effect, p < 0.001). Salivary markers of stress, GI, and time to complete the S&R (∼10 minutes) did not differ between trials, although KME ingestion resulted in significantly higher RPE after the live-burn S&R (KME,6 ± 1; PLA, 4 ± 1). However, POMS data showed the KME also lowered subjective states of nervousness (KME, 0.0 ± 0.0; PLA, 0.6 ± 0.8) and anxiety (KME, 0.0 ± 0.0; PLA, 0.6 ± 0.7) before the S&R (all p < 0.05; large effect sizes). Compared with PLA, ingestion of a KME by firefighters did not mitigate the rise in various markers of salivary stress or impact physical performance during a live-burn S&R. However, differences in RPE and POMS variables were observed, suggesting a possible cognitive role for ßHB.

A 3-Week, Low-Carbohydrate, High-Fat Diet Improves Multiple Serum Inflammatory Markers in Endurance-Trained Males.

ABSTRACT: Waldman, HS, Heatherly, AJ, Killen, LG, Hollingsworth, A, Koh, Y, and O'Neal, EK. A three-week, low-carbohydrate, high-fat diet improves multiple serum inflammatory markers in endurance-trained males. J Strength Cond Res 36(9): 2502-2508, 2022-This study examined the effects of a low-carbohydrate, high-fat diet (LCHF) on inflammatory marker responses in middle-aged endurance athletes. Eight male runners maintained their habitual mixed diet (HMD) in the first phase of the study before switching to a noncalorically restricted LCHF diet (∼70% of kcals from fat; carbohydrate <50 g) for 3 weeks. Subjects completed a 50-minute fixed pace treadmill running protocol in a hot environment, followed by a 5-km outdoor time trial. Fasting serum samples were collected immediately after exercise and heat stress restriction, and again 24 hours after the exercise/heat stressor. Thirty inflammation markers were assessed using the multiplex flow immunoassay technique. Seven markers (BAFF/TNFSF-13, sCD30/TNFRSF8, sCD163, Chitinase3-like1, gp130SIL-6Rß, sTNFR-1, and sTNFR-2) reached statistical significance ( p < 0.05) favoring LCHF before exercise, and sCD30/TNFRSF8 favored ( p < 0.05) LCHF before (HMD = 459 ± 111; LCHF = 296 ± 100) and after (HMD = 385 ± 104; LCHF = 285 ± 104 pg·ml -1 ) exercise. Although the current dietary intervention was short in duration, LCHF seems to offer some protection against multiple chronic inflammation markers for physically active men between ages 30 and 50 years.