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Abstract We consider phenomenological aspects of a natural class of Standard Model-like supersymmetric F-theory vacua realized through flux breaking of rigid E 7 gauge factors. Three generations of Standard Model matter are realized in many of these vacua. We further find that many other Standard Model-like features are naturally compatible with these constructions. For example, dimension-4 and 5 terms associated with proton decay are ubiquitously suppressed. Many of these features are due to the group theoretical structure of E 7 and associated F-theory geometry. In particular, a set of approximate global symmetries descends from the E 7 group, leading to exponential suppression of undesired couplings.

Abstract We use the recently developed methods of arXiv:2108.07810 to analyze vertical flux backgrounds and associated chiral matter spectra in the 4D universal (SU(3) × SU(2) × U(1))/ℤ 6 model introduced in arXiv:1912.10991, which is believed to describe the most generic family of F-theory vacua with tuned (SU(3) × SU(2) × U(1))/ℤ 6 gauge symmetry. Our analysis focuses on a resolution of a particular presentation of the (SU(3) × SU(2) × U(1))/ℤ 6 model in which the elliptic fiber is realized as a cubic in ℙ 2 fibered over an arbitrary smooth threefold base. We show that vertical fluxes can produce nonzero multiplicities for all chiral matter families that satisfy 4D anomaly cancellation, which include as a special case the chiral matter families of the Minimal Supersymmetric Standard Model.

Abstract We study the massless charged spectrum of U(1) gauge fields in F-theory that arise from flux breaking of a nonabelian group. The U(1) charges that arise in this way can be very large. In particular, using vertical flux breaking, we construct an explicit 4D F-theory model with a U(1) decoupled from other gauge sectors, in which the massless/light fields have charges as large as 657. This result greatly exceeds prior results in the literature. We argue heuristically that this result may provide an upper bound on charges for light fields under decoupled U(1) factors in the F-theory landscape. We also show that the charges can be even larger when the U(1) is coupled to other gauge groups.

Abstract Trophic rewilding is increasingly being used to promote megafauna reintroductions to island ecosystems, yet ecosystem response to population restoration once megafauna reintroduction occurs remains understudied. In this study of a population of Galapagos giant tortoises reintroduced to an arid island, tortoise exclosures monitored over an 8‐year‐long period revealed that, in response to the presence of tortoises, herbaceous plant cover and numbers of regenerating woody plants decreased, whereas extent of grass cover increased. Vegetation mapping over a 15‐year‐long period across the island indicated a threshold density of 1–2 tortoises per hectare halted incursion of woody plants and triggered a shift in this savannah‐type ecosystem toward more grasses. Restoration of this giant tortoise population has shaped plant communities at both local and landscape scales with cascading effects on many components of biodiversity on the island.

Abstract A consequence of over 400 years of human exploitation of Galápagos tortoises (Chelonoidis niger ssp.) is the extinction of several subspecies and the decimation of others. As humans captured, killed, and/or removed tortoises for food, oil, museums, and zoos, they also colonized the archipelago resulting in the introduction of invasive plants, animals, and manipulated landscapes for farming, ranching, and infrastructure. Given current conservation and revitalization efforts for tortoises and their habitats, here we investigate nineteenth and twentieth century Galápagos tortoise dietary ecology using museum and archaeological specimens coupled with analysis of carbon (δ13Ccollagen and δ13Capatite), nitrogen (δ15N), hydrogen (δD) and oxygen (δ18Oapatite) stable isotopes and radiocarbon dating. We identify that Galápagos tortoise diets vary between and within islands over time, and that long-term anthropogenic impacts influenced change in tortoise stable isotope ecology by using 57 individual tortoises from 10 different subspecies collected between 1833 and 1967—a 134-year period. On lower elevation islands, which are often hotter and drier, tortoises tend to consume more C4 vegetation (cacti and grasses). Our research suggests human exploitation of tortoises and anthropogenic impacts on vegetation contributed to the extinction of the Floreana Island tortoise (C. n. niger) in the 1850s.

Abstract We give a general description of gauge symmetry breaking using vertical and remainder fluxes in 4D F-theory models. The fluxes can break a geometric gauge group to a smaller group and induce chiral matter, even when the larger group admits no chiral matter representations. We focus specifically on applications to realizations of the Standard Model gauge group and chiral matter spectrum through breaking of rigid exceptional gauge groups E 7 , E 6, which are ubiquitous in the 4D F-theory landscape. Supplemented by an intermediate SU(5) group, these large classes of models give natural constructions of Standard Model-like theories with small numbers of generations of matter in F-theory.

Based on genomic data, the Galapagos giant tortoise species native to Fernandina Island appears to be alive and well, survived by at least one female after being considered extinct since 1906.

Abstract We prove that, for every 6D supergravity theory that has an F-theory description, the property of charge completeness for the connected component of the gauge group (meaning that all charges in the corresponding charge lattice are realized by massive or massless states in the theory) is equivalent to a standard assumption made in F-theory for how geometry encodes the global gauge theory by means of the Mordell-Weil group of the elliptic fibration. This result also holds in 4D F-theory constructions for the parts of the gauge group that come from sections and from 7-branes. We find that in many 6D F-theory models the full charge lattice of the theory is generated by massless charged states; this occurs for each gauge factor where the associated anomaly coefficient satisfies a simple positivity condition. We describe many of the cases where this massless charge sufficiency condition holds, as well as exceptions where the positivity condition fails, and analyze the related global structure of the gauge group and associated Mordell-Weil torsion in explicit F-theory models.

The persistence of virtually every single species depends on both the presence of other species and the specific environmental conditions in a given location. Because in natural settings many of these conditions are unknown, research has been centered on finding the fraction of possible conditions (probability) leading to species coexistence. The focus has been on the persistence probability of an entire multispecies community (formed of either two or more species). However, the methodological and philosophical question has always been whether we can observe the entire community and, if not, what the conditions are under which an observed subset of the community can persist as part of a larger multispecies system. Here, we derive long-term (using analytical calculations) and short-term (using simulations and experimental data) system-level indicators of the effect of third-party species on the coexistence probability of a pair (or subset) of species under unknown environmental conditions. We demonstrate that the fraction of conditions incompatible with the possible coexistence of a pair of species tends to become vanishingly small within systems of increasing numbers of species. Yet, the probability of pairwise coexistence in isolation remains approximately the expected probability of pairwise coexistence in more diverse assemblages. In addition, we found that when third-party species tend to reduce (resp. increase) the coexistence probability of a pair, they tend to exhibit slower (resp. faster) rates of competitive exclusion. Long-term and short-term effects of the remaining third-party species on all possible specific pairs in a system are not equally distributed, but these differences can be mapped and anticipated under environmental uncertainty.

Abstract We observe that in many F-theory models, tuning a specific gauge group G and matter content M under certain circumstances leads to an automatic enhancement to a larger gauge group G′ ⊃ G and matter content M′ ⊃ M. We propose that this is true for any theory G, M whenever there exists a containing theory G′, M′ that cannot be Higgsed down to G, M. We give a number of examples including non-Higgsable gauge factors, nonabelian gauge factors, abelian gauge factors, and exotic matter. In each of these cases, tuning an F-theory model with the desired features produces either an enhancement or an inconsistency, often when the associated anomaly coefficient becomes too large. This principle applies to a variety of models in the apparent 6D supergravity swampland, including some of the simplest cases with U(1) and SU(N) gauge groups and generic matter, as well as infinite families of U(1) models with higher charges presented in the prior literature, potentially ruling out all these apparent swampland theories.

Background Declines of large-bodied herbivorous reptiles are well documented, but the consequences for ecosystem function are not. Understanding how large-bodied herbivorous reptiles engineer ecosystems is relevant given the current interest in restoration of tropical islands where extinction rates are disproportionately high and reptiles are prominent as herbivores. Methods In this study, we measured the ecosystem-level outcomes of long-term quasi-experiment represented by two adjacent islands within the Galapagos Archipelago, one with and the other without Galapagos land iguanas (Conolophus subcristatus), large-bodied herbivores known to feed on many plant species. We characterized plant communities on each island by developing high-resolution (

Abstract We construct a general form for an F-theory Weierstrass model over a general base giving a 6D or 4D supergravity theory with gauge group (SU(3) × SU(2) × U(1))/ℤ6 and generic associated matter, which includes the matter content of the standard model. The Weierstrass model is identified by unHiggsing a model with U(1) gauge symmetry and charges q ≤ 4 previously found by the first author. This model includes two distinct branches that were identified in earlier work, and includes as a special case the class of models recently studied by Cvetič, Halverson, Lin, Liu, and Tian, for which we demonstrate explicitly the possibility of unification through an SU(5) unHiggsing. We develop a systematic methodology for checking that a parameterized class of F-theory Weierstrass models with a given gauge group G and fixed matter content is generic (contains all allowed moduli) and confirm that this holds for the models constructed here.

Abstract We find through a systematic analysis that all but 29,223 of the 473.8 million 4D reflexive polytopes found by Kreuzer and Skarke have a 2D reflexive subpolytope. Such a subpolytope is generally associated with the presence of an elliptic or genus one fibration in the corresponding birational equivalence class of Calabi-Yau threefolds. This extends the growing body of evidence that most Calabi-Yau threefolds have an elliptically fibered phase.

ABSTRACT Purpose: To evaluate the low-level laser therapy (LLLT) on the membrane induced by the Masquelet technique in rabbits. Methods: Twelve Norfolk rabbits at approximately 3 months of age were used. A 1-cm segmental defect was induced in both radii, which were filled with polymethylmethacrylate cylinder. LLLT was used postoperatively in the bone defect of one of the forelimbs every 48 hours for 15 days. Six rabbits were euthanatized on third and sixth postoperative weeks. Results: In both forelimbs, radiographs showed new bone growth from radius cut ends on the third postoperative week and more advanced stage on the sixth postoperative week. Ultrasound showed induced membrane one week after the surgery. Histologically, there were no significant differences in the semi-quantitative score of inflammation intensity, total number of blood vessels, bone metaplasia, and collagen. The average thicknesses were 2,050.17 and 1,451.96 μm for control membranes and 2,724.26 and 2,081.03 μm for irradiated membranes, respectively, on third and sixth postoperative weeks. Vascular endothelial growth factor A (VEGF-A) and platelet derived growth factor (PDGF) expression were present in the induced membranes of control and irradiated forelimbs, but there was no significant difference. Conclusions: Based on assessment methods, it was not possible to demonstrate the effect of LLLT on the induced membrane.

Abstract In six-dimensional supergravity, there is a natural sense in which matter lying in certain representations of the gauge group is “generic,” in that other “exotic” matter representations require more fine tuning. From considerations of the dimensionality of the moduli space and anomaly cancellation conditions, we find that the generic sets of matter representations are well-defined for 6D supergravity theories with gauge groups containing arbitrary numbers of nonabelian factors and U(1) factors. These generic matter representations also match with those that arise in the most generic F-theory constructions, both in 6D and in 4D, with non-generic matter representations requiring more exotic singularity types. The analysis of generic versus exotic matter illuminates long-standing puzzles regarding F-theory models with multiple U(1) factors and provides a useful framework for analyzing the 6D “swampland” of apparently consistent low-energy theories that cannot be realized through known string constructions. We note also that the matter content of the standard model is generic by the criteria used here only if the global structure is SU(3)c × SU(2)L × U(1) Y /ℤ6.

Abstract We find that for many Calabi-Yau threefolds with elliptic or genus one fibrations mirror symmetry factorizes between the fiber and the base of the fibration. In the simplest examples, the generic CY elliptic fibration over any toric base surface B that supports an elliptic Calabi-Yau threefold has a mirror that is an elliptic fibration over a dual toric base surface B ˜ $$ \tilde{B} $$ that is related through toric geometry to the line bundle −6K B . The Kreuzer-Skarke database includes all these examples and gives a wide range of other more complicated constructions where mirror symmetry also factorizes. Since recent evidence suggests that most Calabi-Yau threefolds are elliptic or genus one fibered, this points to a new way of understanding mirror symmetry that may apply to a large fraction of smooth Calabi-Yau threefolds. The factorization structure identified here can also apply for CalabiYau manifolds of higher dimension.

Abstract We systematically analyze the fibration structure of toric hypersurface Calabi-Yau threefolds with large and small Hodge numbers. We show that there are only four such Calabi-Yau threefolds with h 1,1 ≥ 140 or h 2,1 ≥ 140 that do not have manifest elliptic or genus one fibers arising from a fibration of the associated 4D polytope. There is a genus one fibration whenever either Hodge number is 150 or greater, and an elliptic fibration when either Hodge number is 228 or greater. We find that for small h 1,1 the fraction of polytopes in the KS database that do not have a genus one or elliptic fibration drops exponentially as h 1,1 increases. We also consider the different toric fiber types that arise in the polytopes of elliptic Calabi-Yau threefolds.

Abstract We compare the sets of Calabi-Yau threefolds with large Hodge numbers that are constructed using toric hypersurface methods with those can be constructed as elliptic fibrations using Weierstrass model techniques motivated by F-theory. There is a close correspondence between the structure of “tops” in the toric polytope construction and Tate form tunings of Weierstrass models for elliptic fibrations. We find that all of the Hodge number pairs (h 1,1, h 2,1) with h 1,1 or h 2,1 ≥ 240 that are associated with threefolds in the Kreuzer-Skarke database can be realized explicitly by generic or tuned Weierstrass/Tate models for elliptic fibrations over complex base surfaces. This includes a relatively small number of somewhat exotic constructions, including elliptic fibrations over non-toric bases, models with new Tate tunings that can give rise to exotic matter in the 6D F-theory picture, tunings of gauge groups over non-toric curves, tunings with very large Hodge number shifts and associated nonabelian gauge groups, and tuned Mordell-Weil sections associated with U(1) factors in the corresponding 6D theory.

Abstract We show that massless fields with large abelian charges (up to at least q = 21) can be constructed in 6D F-theory models with a U(1) gauge group. To show this, we explicitly construct F-theory Weierstrass models with nonabelian gauge groups that can be broken to U(1) theories with a variety of large charges. Determining the maximum abelian charge allowed in such a theory is key to eliminating what seems currently to be an infinite swampland of apparently consistent U(1) supergravity theories with large charges.

Abstract We analyze the anomaly constraints on 6D supergravity theories with a single abelian U(1) gauge factor. For theories with charges restricted to q = ±1, ±2 and no tensor multiplets, anomaly-free models match those models that can be realized from F-theory compactifications almost perfectly. For theories with tensor multiplets or with larger charges, the F-theory constraints are less well understood. We show, however, that there is an infinite class of distinct massless charge spectra in the “swampland” of theories that satisfy all known quantum consistency conditions but do not admit a realization through F-theory or any other known approach to string compactification. We also compare the spectra of charged matter in abelian theories with those that can be realized from breaking nonabelian SU(2) and higher rank gauge symmetries.

Abstract Using a one-way Monte Carlo algorithm from several different starting points, we get an approximation to the distribution of toric threefold bases that can be used in four-dimensional F-theory compactification. We separate the threefold bases into “resolvable” ones where the Weierstrass polynomials (f, g) can vanish to order (4, 6) or higher on codimension-two loci and the “good” bases where these (4, 6) loci are not allowed. A simple estimate suggests that the number of distinct resolvable base geometries exceeds 103000, with over 10250 “good” bases, though the actual numbers are likely much larger. We find that the good bases are concentrated at specific “end points” with special isolated values of h 1,1 that are bigger than 1,000. These end point bases give Calabi-Yau fourfolds with specific Hodge numbers mirror to elliptic fibrations over simple threefolds. The non-Higgsable gauge groups on the end point bases are almost entirely made of products of E 8, F 4, G 2 and SU(2). Nonetheless, we find a large class of good bases with a single non-Higgsable SU(3). Moreover, by randomly contracting the end point bases, we find many resolvable bases with h 1,1(B) ∼ 50-200 that cannot be contracted to another smooth threefold base.

Abstract We analyze exotic matter representations that arise on singular seven-brane configurations in F-theory. We develop a general framework for analyzing such representations, and work out explicit descriptions for models with matter in the 2-index and 3-index symmetric representations of SU(N) and SU(2) respectively, associated with double and triple point singularities in the seven-brane locus. These matter representations are associated with Weierstrass models whose discriminants vanish to high order thanks to nontrivial cancellations possible only in the presence of a non-UFD algebraic structure. This structure can be described using the normalization of the ring of intrinsic local functions on a singular divisor. We consider the connection between geometric constraints on singular curves and corresponding constraints on the low-energy spectrum of 6D theories, identifying some new examples of apparent “swampland” theories that cannot be realized in F-theory but have no apparent low-energy inconsistency.

A major step in the development of conservation measures would be to study and understand the sources of non-natural mortality in wild fauna. The implementation of such measures should be a priority in oceanic islands because biodiversity hotspots are concentrated in these locations. Furthermore, anthropogenic changes have a greater impact on island species than on their mainland relatives. This situation is of particular relevance in the Galápagos Archipelago, owing to its rapid population growth and the striking increase in the number of vehicles. The latter aspect is due to attempts by the tourist industry to stimulate the economy in this area. Thus, the environment and biota are under new pressures. There are few studies on the effects of wildlife roadkill in the Galápagos. We surveyed two stretches of a 13.8-km road in two different vegetation zones on the island of Santa Cruz. This island has the highest population and the greatest number of tourists in the archipelago. We determined the spatial patterns of bird roadkill using counts, which were conducted via bicycle rides. We recorded 168 carcasses comprising seven species (six native and one invasive). Roadkill did not occur at the same rate over the two stretches: it was significantly higher over Stretch 1, which had a greater volume of traffic. Neither were species equally distributed over the stretches. We identified a high-mortality black spot within Stretch 1 in an area in which high-speed traffic may have contributed strongly to roadkill. We also estimated the carcass disappearance rate to better determine the roadkill rate. Data on the disappearance rate could be of help in the design and implementation of future studies. This study presents the first data on the road mortality rate in the Galápagos Islands, finding that it is much higher than in other natural areas. This represents a first step toward minimizing the growing threat to Galápagos birds, and provides a basis for future research on conservation management plans in the Galápagos Islands.

Abstract A species of Galápagos tortoise endemic to Española Island was reduced to just 12 females and three males that have been bred in captivity since 1971 and have produced over 1700 offspring now repatriated to the island. Our molecular genetic analyses of juveniles repatriated to and surviving on the island indicate that none of the tortoises sampled in 1994 had hatched on the island versus 3% in 2004 and 24% in 2007, which demonstrates substantial and increasing reproduction in situ once again. This recovery occurred despite the parental population having an estimated effective population size

Most otariids have colony-specific foraging areas during the breeding season, when they behave as central place foragers. However, they may disperse over broad areas after the breeding season and individuals from different colonies may share foraging grounds at that time. Here, stable isotope ratios in the skull bone of adult Galapagos sea lions (Zalophus wollebaeki) were used to assess the long-term fidelity of both sexes to foraging grounds across the different regions of the Galapagos archipelago. Results indicated that the stable isotope ratios (δ(13)C and δ(15)N) of sea lion bone significantly differed among regions of the archipelago, without any significant difference between sexes and with a non significant interaction between sex and region. Moreover, standard ellipses, estimated by Bayesian inference and used as a measure of the isotopic resource use area at the population level, overlapped widely for the sea lions from the southern and central regions, whereas the overlap of the ellipses for sea lions from the central and western regions was small and non-existing for those from the western and southern regions. These results suggest that males and females from the same region within the archipelago use similar foraging grounds and have similar diets. Furthermore, they indicate that the exchange of adults between regions is limited, thus revealing a certain degree of foraging philopatry at a regional scale within the archipelago. The constraints imposed on males by an expanded reproductive season (~ 6 months), resulting from the weak reproductive synchrony among females, and those imposed on females by a very long lactation period (at least one year but up to three years), may explain the limited mobility of adult Galapagos sea lions of both sexes across the archipelago.

The taxonomy of giant Galapagos tortoises (Chelonoidis spp.) is currently based primarily on morphological characters and island of origin. Over the last decade, compelling genetic evidence has accumulated for multiple independent evolutionary lineages, spurring the need for taxonomic revision. On the island of Santa Cruz there is currently a single named species, C. porteri. Recent genetic and morphological studies have shown that, within this taxon, there are two evolutionarily and spatially distinct lineages on the western and eastern sectors of the island, known as the Reserva and Cerro Fatal populations, respectively. Analyses of DNA from natural populations and museum specimens, including the type specimen for C. porteri, confirm the genetic distinctiveness of these two lineages and support elevation of the Cerro Fatal tortoises to the rank of species. In this paper, we identify DNA characters that define this new species, and infer evolutionary relationships relative to other species of Galapagos tortoises.

Among introduced species in the Galápagos are three species of geckos – Gonatodes caudiscutatus, Lepidodactylus lugubris, Phyllodactylus reissii – occurring on the islands of Isabela, San Cristóbal, and Santa Cruz. Here we report the first record of a fourth invasive species of gecko from Isabela, as well as the first record of P. reissii from the same island.

BackgroundAntibiotic resistance, evolving and spreading among bacterial pathogens, poses a serious threat to human health. Antibiotic use for clinical, veterinary and agricultural practices provides the major selective pressure for emergence and persistence of acquired resistance determinants. However, resistance has also been found in the absence of antibiotic exposure, such as in bacteria from wildlife, raising a question about the mechanisms of emergence and persistence of resistant strains under similar conditions, and the implications for resistance control strategies. Since previous studies yielded some contrasting results, possibly due to differences in the ecological landscapes of the studied wildlife, we further investigated this issue in wildlife from a remote setting of the Galapagos archipelago.Methodology/principal findingsScreening for acquired antibiotic resistance was carried out in commensal enterobacteria from Conolophus pallidus, the terrestrial iguana of Isla Santa Fe, where: i) the abiotic conditions ensure to microbes good survival possibilities in the environment; ii) the animal density and their habits favour microbial circulation between individuals; and iii) there is no history of antibiotic exposure and the impact of humans and introduced animal species is minimal except for restricted areas. Results revealed that acquired antibiotic resistance traits were exceedingly rare among bacteria, occurring only as non-dominant strains from an area of minor human impact.Conclusions/significanceWhere both the exposure to antibiotics and the anthropic pressure are minimal, acquired antibiotic resistance traits are not normally found in bacteria from wildlife, even if the ecological landscape is highly favourable to bacterial circulation among animals. Monitoring antibiotic resistance in wildlife from remote areas could also be a useful tool to evaluate the impact of anthropic pressure.

Although not unusual to find captive relicts of species lost in the wild, rarely are presumed extinct species rediscovered outside of their native range. A recent study detected living descendents of an extinct Galápagos tortoise species (Chelonoidis elephantopus) once endemic to Floreana Island on the neighboring island of Isabela. This finding adds to the growing cryptic diversity detected among these species in the wild. There also exists a large number of Galápagos tortoises in captivity of ambiguous origin. The recently accumulated population-level haplotypic and genotypic data now available for C. elephantopus add a critical reference population to the existing database of 11 extant species for investigating the origin of captive individuals of unknown ancestry.We reanalyzed mitochondrial DNA control region haplotypes and microsatellite genotypes of 156 captive individuals using an expanded reference database that included all extant Galápagos tortoise species as well as the extinct species from Floreana. Nine individuals (six females and three males) exhibited strong signatures of Floreana ancestry and a high probability of assignment to C. elephantopus as detected by Bayesian assignment and clustering analyses of empirical and simulated data. One male with high assignment probability to C. elephantopus based on microsatellite genotypic data also possessed a "Floreana-like" mitochondrial DNA haplotype.Historical DNA analysis of museum specimens has provided critical spatial and temporal components to ecological, evolutionary, taxonomic and conservation-related research, but rarely has it informed ex situ species recovery efforts. Here, the availability of population-level genotypic data from the extinct C. elephantopus enabled the identification of nine Galápagos tortoise individuals of substantial conservation value that were previously misassigned to extant species of varying conservation status. As all captive individuals of C. elephantopus ancestry currently reside at a centralized breeding facility on Santa Cruz, these findings permit breeding efforts to commence in support of the reestablishment of this extinct species to its native range.

The Galapagos Islands are among the most renowned natural sites in the world. Unlike other oceanic archipelagos, the ecological and evolutionary processes characteristic of Galapagos have been minimally affected by human activities, and the archipelago still retains most of its original, unique biodiversity. However, several recent reports suggest that the development model has turned unsustainable and that the unique values of the archipelago might be seriously at risk. In response to international concern, UNESCO added Galapagos to the list of World Heritage in Danger in 2007. Our goal was to provide new insights into the origins of the present-day crisis and suggest possible management alternatives. To this end, we re-examined the Galapagos situation from a broad systems perspective, conceptualizing the archipelago as a complex social-ecological system. Past, present, and possible future trends were explored using the resilience theory as a perspective for understanding the dynamics of the system. Four major historical periods were characterized and analyzed using Holling's adaptive cycle metaphor. The current Galapagos situation was characterized as a prolonged series of crisis events followed by renewal attempts that have not yet been completed. Three plausible future scenarios were identified, with tourism acting as the primary driver of change. The current tourism model reduces the system's resilience through its effects on the economy, population growth, resource consumption, invasive species arrival, and lifestyle of the island residents. Opportunities to reorganize and maintain a desirable state do exist. However, strong political and management decisions are urgently needed to avoid an irreversible shift to a socially and environmentally undesirable regime. Key measures to achieve a new sustainability paradigm for Galapagos include modifying traditional practices to produce a more adaptive resilience-based co-management model, adopting a more comprehensive approach to territorial planning, strengthening participative approaches and institutional networks, and promoting transdisciplinary research at the frontiers of social and biophysical sciences.

Abstract The rio da Dona is an important water body in the Recôncavo Sul basin used as a water supply for the neighboring towns and for agriculture, recreation and subsistence fishing. The knowledge about the ichthyofauna of this river is scarce. In this paper, an inventory of the fish fauna from rio da Dona basin and an identification key for the species recorded are presented. Additionally, taxonomic and conservationist issues are discussed. The specimens were collected in different sites along the upper, middle and lower courses of the rio da Dona. The fishes were anesthetized, fixed in formalin, conserved in ethanol, and identified. In addition to the material collected, specimens previously deposited in the ichthyological collection of the Museu de História Natural da Bahia were also analyzed. Twenty species, distributed into 16 genera, ten families, and four orders were recorded. One of these species, Aspidoras kiriri, is endemic to the rio da Dona. Four species, Cichla pinima, Coptodon rendalli, Poecilia reticulata and Serrasalmus brandtii, have been introduced into the river. Higher richness of native species has been recorded in the upper course of the rio da Dona, while in the middle and lower parts non-native species were also representative. Along the river, a series of anthropic impacts were observed, such as deforestation of native forest including the riparian vegetation, silting and dams, which can probably compromised the resident ichthyofauna.

Background: Pre-exposure Prophylaxis (PrEP) medication is the keystone of preventative measures to curtail the spread of HIV. However, oral PrEP, the pill intended to prevent HIV, has been slow to proliferate among men who have sex with men (MSM). This is of major concern as MSM account for the largest number of new HIV diagnoses in the U.S. More recently, the newest generation of PrEP in the form of a long-acting injectable (LAI) is to be administered every two months as an intramuscular injection and many MSM indicate preferring LAI-PrEP to the oral form of PrEP. However, uptake of PrEP, in all forms, remains low. Research is sparse that focuses on LAI-PrEP uptake among Black/African American and Latinx men who have sex with men (BLMSM)., Objective: To address this concern, this study explored the willingness to uptake LAI-PrEP, and recommendations for increasing awareness and encouraging uptake of LAI-PrEP among BLMSM., Methods: Qualitative data were collected between February 2022 to December 2022 through focus groups via Zoom with BLMSM (N=30; Black=14, Latinx=16) aged 18 to 29 (Mean = 23, SD = 3) in Los Angeles County., Results: Findings revealed that while 90% of BLMSM were aware of PrEP in oral form, only 10% were aware of LAI-PrEP. Findings from the qualitative analysis suggested to consider self-administration of LAI-PrEP, allow local community pharmacists to assess and administer it, and promote uptake of LAI-PrEP using high-profile male content creators and stars on OnlyFans social media platform., Conclusion: Increasing PrEP uptake, in all forms available, such as promoting awareness through popular social media stars, and engaging community pharmacists in feasible ways, is critical for addressing the disproportionate impact of HIV among the BLMSM community., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Very little research has examined suicidal ideation or the factors associated with contemplating suicide among older transgender adults. This paper examines whether or not there is evidence of syndemic effects influencing suicidal ideation among transgender persons aged 50 or older., Methods: Data from the 2015 U.S. National Transgender Survey were used to examine five domains of potentially-syndemic effects (workplace issues, interactions with professionals, using public services, personal safety, and socioeconomic disadvantages) in a sample of 3,724 transgender Americans aged 50 or older. A dichotomous measure of suicidal ideation during the past year was the main outcome measure., Results: The odds of contemplating suicide increased anywhere from 96% to 121% among people experiencing any of the problems under study, and anywhere from 258% to 1,552% (depending upon the syndemic effect domain in question) when they were faced by all of the experiences included in any particular domain. When all items were combined, exposure to any of the domains' problems elevated the risk of contemplating suicide by 276% and exposure to all of the problems examined increased the risk by 861%. The syndemic effects measure remained significant in multivariate analysis controlling for the influence of other potentially-relevant factors., Conclusions: Considerable evidence for the presence of syndemic effects was found, demonstrating that the more different types of adverse conditions that older transgender person's face, the more likely they are to experience to contemplate suicide. There is evidence that these effects diminish with advancing age.

Purpose: Using a minority stress paradigm, this paper examines the relationship between anti-transgender discrimination, harassment, and violence among transgender adults. Methods: Data from the 2015 U.S. National Transgender Survey were used to examine twenty types of anti-transgender experiences/problems (e.g., harassment at work, problems with police officials, verbal and physical assaults) in a sample of 27,715 transgender Americans aged 18 or older. Binge drinking during the previous month was the dependent variable, and eight control measures were examined in the multivariate analysis. Results: Experiencing any of the twenty types of anti-transgender discrimination, harassment, or violence increased the odds of binge drinking by 48%. Experiencing many such problems increased the odds of binge drinking by 104%. Multivariate analysis showed that anti-transgender discrimination, harassment, and violence remains a predictor of binge drinking even when other key measures are taken into account. Younger people, racial minority group members, and persons who were not married or "involved" were at particularly great risk. Conclusions: Consistent with the minority stress paradigm, the more different types of anti-transgender experiences people had, the more likely they were to engage in binge drinking. Targeted intervention needs to help transgender persons to avoid anti-transgender discrimination, harassment, and violence to the greatest extent possible, and to develop resiliency skills whenever they are victimized. This is particularly true for transgender persons who are younger, minority, and not "involved" in a relationship.

Purpose: This paper examines the relationships among transition milestones (i.e., transition-related events in transgender persons' lives that demarcate their life circumstances before vs. afte a milestone was reached), psychological distress, and suicidal ideation in a large sample of transgender adults., Methods: Data from the 2015 U.S. National Transgender Survey were used to examine 11 specific transition milestones in a sample of 27,715 transgender Americans aged 18 or older. The Kessler-6 scale was used to measure psychological distress and a dichotomous measure of suicidal ideation during the past year was the other main outcome measure. Covariates in the multivariate analysis included demographic measures, variables assessing support and discrimination, and 11 transition milestones., Results: Bivariate analyses revealed that, in almost all instances, reaching specific transition milestones led to reduced psychological distress and diminished odds of suicidal ideation. Multivariate analysis revealed that psychological distress was a strong predictor of suicidal ideation, but transition milestones were not retained in the final model. Structural equation analysis showed that three specific transition milestones (namely, changing one's name and/or gender on legal documents, taking gender-affirming hormones, having had any gender-conforming surgical procedures) influenced suicidal ideation indirectly, through their direct impact on psychological distress., Conclusions: Reaching specific transition milestones plays an important role in many transgender adults' lives, and may be highly beneficial in helping them to reduce psychological distress. This, in turn, is likely to have a positive impact upon their likelihood of contemplating suicide., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: This paper examines the conjoint effects of serious psychological distress, suicidal ideation, and substance abuse among transgender adults. The principal aims are to determine the prevalence of this "triple whammy," identify the factors underlying the co-occurrence of all three problems, and to determine if there is evidence of syndemic effects underlying the "triple whammy.", Methods: Data from the 2015 U.S. National Transgender Survey were used to examine the "triple whammy" relationship in a sample of 27,715 transgender Americans aged 18 or older. Odds ratios and multivariate logistic regression were performed to examine the data., Results: 13.3 % of the study participants reported experiencing serious psychological distress, suicidal ideation, and substance abuse. The most potent predictors of the "triple whammy" were younger age, a greater number of anti-transgender experiences, and not reaching various transition milestones. Strong evidence emerged to indicate the presence of syndemic effects in operation., Conclusions: Experiencing the combination of adverse mental health and substance abuse was not uncommon in this population of transgender adults. Being young, experiencing a larger variety of types of anti-transgender discrimination, harassment, and violence, and not reaching specific transition milestones all had a significant impact on the odds that people would experience the "triple whammy." This was particularly true when these measures were examined in conjunction with one another, because of strong syndemic effects., Competing Interests: Declaration of competing interest Neither author has any conflicts of interest to report with regard to this research., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Disuse-induced muscle atrophy is a common clinical problem observed mainly in older adults, intensive care units patients, or astronauts. Previous studies presented biological sex divergence in progression of disuse-induced atrophy along with differential changes in molecular mechanisms possibly underlying muscle atrophy. The aim of this study was to perform transcriptomic profiling of male and female mice during the onset and progression of unloading disuse-induced atrophy. Male and female mice underwent hindlimb unloading (HU) for 24, 48, 72, and 168 h ( n = 8/group). Muscles were weighed for each cohort and gastrocnemius was used for RNA-sequencing analysis. Females exhibited muscle loss as early as 24 h of HU, whereas males after 168 h of HU. In males, pathways related to proteasome degradation were upregulated throughout 168 h of HU, whereas in females these pathways were upregulated up to 72 h of HU. Lcn2 , a gene contributing to regulation of myogenesis, was upregulated by 6.46- to 19.86-fold across all time points in females only. A reverse expression of Fosb , a gene related to muscle degeneration, was observed between males (4.27-fold up) and females (4.57-fold down) at 24-h HU. Mitochondrial pathways related to tricarboxylic acid (TCA) cycle were highly downregulated at 168 h of HU in males, whereas in females this downregulation was less pronounced. Collagen-related pathways were consistently downregulated throughout 168 h of HU only in females, suggesting a potential biological sex-specific protective mechanism against disuse-induced fibrosis. In conclusion, females may have protection against HU-induced skeletal muscle mitochondrial degeneration and fibrosis through transcriptional mechanisms, although they may be more vulnerable to HU-induced muscle wasting compared with males. NEW & NOTEWORTHY Herein, we have assessed the transcriptomic response across biological sexes during the onset and progression of unloading disuse-induced atrophy in mice. We have demonstrated an inverse expression of Fosb between males and females, as well as differentially timed patterns of expressing atrophy-related pathways between sexes that are concomitant to the accelerated atrophy in females. We also identified in females signs of mechanisms to combat disuse-induced mitochondrial degeneration and fibrosis.

Cancer cachexia (CC) is a multifactorial wasting syndrome characterized by a significant loss in lean and/or fat mass and represents a leading cause of mortality in cancer patients. Nutraceutical treatments have been proposed as a potential treatment strategy to mitigate cachexia-induced muscle wasting. However, contradictory findings warrant further investigation. The purpose of this study was to determine the effects of leucine supplementation on skeletal muscle in male and female Apc Min/+ mice (APC). APC mice and their wild-type (WT) littermates were given normal drinking water or 1.5% leucine-supplemented water (n = 4-10/group/sex). We measured the gene expression of regulators of inflammation, protein balance, and myogenesis. Leucine treatment lowered survival rates, body mass, and muscle mass in males, while in females, it had no effect on body or muscle mass. Leucine treatment altered inflammatory gene expression by lowering Il1b 87% in the APC group and decreasing Tnfa 92% in both WT and APC males, while it had no effect in females ( p < 0.05). Leucine had no effect on regulators of protein balance and myogenesis in either sex. We demonstrated that leucine exacerbates moribundity in males and is not sufficient for mitigating muscle or fat loss during CC in either sex in the Apc Min/+ mouse., Competing Interests: The authors declare no conflict of interest.

Cancer cachexia is clinically defined by involuntary weight loss >5% in <6 mo, primarily affecting skeletal muscle. Here, we aimed to identify sex differences in the onset of colorectal cancer cachexia with specific consideration to skeletal muscle contractile and metabolic functions. Eight-weeks old BALB/c mice (69 males, 59 females) received subcutaneous C26 allografts or PBS vehicle. Tumors were developed for 10-, 15-, 20-, or 25 days. Muscles and organs were collected, in vivo muscle contractility, protein synthesis rate, mitochondrial function, and protein turnover markers were assessed. One-way ANOVA within sex and trend analysis between sexes were performed, P < 0.05. Gastrocnemius and tibialis anterior (TA) muscles became atrophic in male mice at 25 days, whereas female mice exhibited no significant differences in muscle weights at endpoints despite presenting hallmarks of cancer cachexia (fat loss, hepatosplenomegaly). We observed lowered muscle contractility and protein synthesis concomitantly to muscle mass decay in males, with higher proteolytic markers in muscles of both sexes. mRNA of Opa1 was lower in TA, whereas Bnip3 was higher in gastrocnemius after 25 days in male mice, with no significant effect in female mice. Our data suggest relative protections to skeletal muscle in females compared with males despite other canonical signs of cancer cachexia and increased protein degradation markers; suggesting we should place onus upon nonmuscle tissues during early stages of cancer cachexia in females. We noted potential protective mechanisms relating to skeletal muscle contractile and mitochondrial functions. Our findings underline possible heterogeneity in onset of cancer cachexia between biological sexes, suggesting the need for sex-specific approaches to treat cancer cachexia. NEW & NOTEWORTHY Our study demonstrates biological-sex differences in phenotypic characteristics of cancer cachexia between male and female mice, whereby females display many common characteristics of cachexia (gonadal fat loss and hepatosplenomegaly), protein synthesis markers alterations, and common catabolic markers in skeletal muscle despite relatively preserved muscle mass in early-stage cachexia compared with males. Mechanisms of cancer cachexia appear to differ between sexes. Data suggest need to place onus of early cancer cachexia detection and treatment on nonmuscle tissues in females.

Background: Cancer-cachexia (CC) is a debilitating condition affecting up to 80% of cancer patients and contributing to 40% of cancer-related deaths. While evidence suggests biological sex differences in the development of CC, assessments of the female transcriptome in CC are lacking, and direct comparisons between sexes are scarce. This study aimed to define the time course of Lewis lung carcinoma (LLC)-induced CC in females using transcriptomics, while directly comparing biological sex differences., Results: We found the global gene expression of the gastrocnemius muscle of female mice revealed biphasic transcriptomic alterations, with one at 1 week following tumor allograft and another during the later stages of cachexia development. The early phase was associated with the upregulation of extracellular-matrix pathways, while the later phase was characterized by the downregulation of oxidative phosphorylation, electron transport chain, and TCA cycle. When DEGs were compared to a known list of mitochondrial genes (MitoCarta), ~ 47% of these genes were differently expressed in females exhibiting global cachexia, suggesting transcriptional changes to mitochondrial gene expression happens concomitantly to functional impairments previously published. In contrast, the JAK-STAT pathway was upregulated in both the early and late stages of CC. Additionally, we observed a consistent downregulation of Type-II Interferon signaling genes in females, which was associated with protection in skeletal muscle atrophy despite systemic cachexia. Upregulation of Interferon signaling was noted in the gastrocnemius muscle of cachectic and atrophic male mice. Comparison of female tumor-bearing mice with males revealed ~ 70% of DEGs were distinct between sexes in cachectic animals, demonstrating dimorphic mechanisms of CC., Conclusion: Our findings suggest biphasic disruptions in the transcriptome of female LLC tumor-bearing mice: an early phase associated with ECM remodeling and a late phase, accompanied by the onset of systemic cachexia, affecting overall muscle energy metabolism. Notably, ~ 2/3 of DEGs in CC are biologically sex-specific, providing evidence of dimorphic mechanisms of cachexia between sexes. Downregulation of Type-II Interferon signaling genes appears specific to CC development in females, suggesting a new biological sex-specific marker of CC not reliant on the loss of muscle mass, that might represent a protective mechanism against muscle loss in CC in female mice., (© 2023. The Author(s).)

Cachexia is characterized by losses in lean body mass and its progression results in worsened quality of life and exacerbated outcomes in cancer patients. However, the role and impact of fibrosis during the early stages and development of cachexia in under-investigated. The purpose of this study was to determine if fibrosis occurs during cachexia development, and to evaluate this in both sexes. Female and male C57BL6/J mice were injected with phosphate-buffered saline or Lewis Lung Carcinoma (LLC) at 8-week of age, and tumors were allowed to develop for 1, 2, 3, or 4 weeks. 3wk and 4wk female tumor-bearing mice displayed a dichotomy in tumor growth and were reassigned to high tumor (HT) and low tumor (LT) groups. In vitro analyses were also performed on cocultured C2C12 and 3T3 cells exposed to LLC conditioned media. Immunohistochemistry and quantitative polymerase chain reaction (qPCR) analysis were used to investigate fibrosis and fibrosis-related signaling in skeletal muscle. Collagen deposition in skeletal muscle was increased in the 1wk, LT, and HT groups in female mice. However, collagen deposition was only increased in the 4wk group in male mice. In general, female mice displayed earlier alterations in extracellular matrix (ECM)-related genes beginning at 1wk post-LLC injection. Whereas this was not seen in males. While overall tumor burden is tightly correlated to cachexia development in both sexes, fibrotic development is not. Male mice did not exhibit early-stage alterations in ECM-related genes contrary to what was noted in female mice., (© 2023 John Wiley & Sons Ltd.)

Cancer cachexia (CC) accounts for 20%-40% of cancer-related deaths. Mitochondrial aberrations have been shown to precede muscle atrophy in different atrophy models, including cancer. Therefore, this study investigated potential protection from the cachectic phenotype through overexpression of peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α). First, to establish potential of mitochondria-based approaches we showed that the mitochondrial antioxidant MitoTEMPO (MitoT) attenuates myotube atrophy induced by Lewis lung carcinoma (LLC) cell conditioned media. Next, cachexia was induced in muscle-specific PGC-1α overexpressing (MCK-PCG1α) or wildtype (WT) littermate mice by LLC implantation. MCK-PCG1α did not protect LLC-induced muscle mass loss. In plantaris, Atrogin mRNA content was 6.2-fold and ∼11-fold greater in WT-LLC vs WT-phosphate-buffered saline (PBS) for males and females, respectively ( p  < 0.05). MitoTimer red:green ratio for male PGC was ∼65% higher than WT groups ( p  < 0.05), with ∼3-fold more red puncta in LLC than PBS ( p  < 0.05). Red:green ratio was ∼56% lower in females WT-LLC vs PGC-LLC ( p  < 0.05). In females, no change in red puncta was noted across conditions. Lc3 mRNA content was ∼73% and 2-fold higher in male and female LLC mice, respectively, vs PBS ( p  < 0.05). While MitoT could mitigate cancer-induced atrophy in vitro, PGC-1α overexpression was insufficient to protect muscle mass and mitochondrial health in vivo despite mitigation of cachexia-associated signaling pathways.

The ability of skeletal muscle to regenerate from injury is crucial for locomotion, metabolic health, and quality of life. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1A) is a transcriptional coactivator required for mitochondrial biogenesis. Increased mitochondrial biogenesis is associated with improved muscle cell differentiation, however PGC1A's role in skeletal muscle regeneration following damage requires further investigation. The purpose of this study was to investigate the role of skeletal muscle-specific PGC1A overexpression during regeneration following damage. 22 C57BL/6J (WT) and 26 PGC1A muscle transgenic (A1) mice were injected with either phosphate-buffered saline (PBS, uninjured control) or Bupivacaine (MAR, injured) into their tibialis anterior (TA) muscle to induce skeletal muscle damage. TA muscles were extracted 3- or 28-days post-injury and analyzed for markers of regenerative myogenesis and protein turnover. Pgc1a mRNA was ∼10-20 fold greater in A1 mice. Markers of protein synthesis, AKT and 4EBP1, displayed decreases in A1 mice compared to WT at both timepoints indicating a decreased protein synthetic response. Myod mRNA was ∼75% lower compared to WT 3 days post-injection. WT mice exhibited decreased cross-sectional area of the TA muscle at 28 days post-injection with bupivacaine compared to all other groups. PGC1A overexpression modifies the myogenic response during regeneration., Competing Interests: The authors do not have any conflicts of interest to declare., (© 2022 Chengdu Sport University. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Cancer cachexia (CC) is a multifactorial syndrome characterised by unintentional loss of body weight and muscle mass in patients with cancer. The major hallmarks associated with CC development and progression include imbalanced protein turnover, inflammatory signalling, mitochondrial dysfunction and satellite cell dysregulation. So far, there is no effective treatment to counteract muscle wasting in patients with CC. Exercise training has been proposed as a potential therapeutic approach for CC. This review provides an overview of the effects of exercise training in CC-related mechanisms as well as how factors such as cancer comorbidities, exercise modality and biological sex can influence exercise effectiveness in CC. Evidence in mice and humans suggests exercise training combats all of the hallmarks of CC. Several exercise modalities induce beneficial adaptations in patients/animals with CC, but concurrent resistance and endurance training is considered the optimal type of exercise. In the case of cancer patients presenting comorbidities, exercise training should be performed only under specific guidelines and precautions to avoid adverse effects. Observational comparison of studies in CC using different biological sex shows exercise-induced adaptations are similar between male and female patients/animals with cancer, but further studies are needed to confirm this.

microRNAs (miRs) are linked to various human diseases including type 2 diabetes mellitus (T2DM) and emerging evidence suggests that miRs may serve as potential therapeutic targets. Lower miR-16 content is consistent across different models of T2DM; however, the role of miR-16 in muscle metabolic health is still elusive. Therefore, the purpose of this study was to investigate how deletion of miR-16 in mice affects skeletal muscle metabolic health and contractile function in both sexes. This study was conducted using both 1 ) in vitro and 2 ) in vivo experiments. In in vitro experiments, we used C2C12 myoblasts to test if inhibition or overexpression of miR-16 affected insulin-mediated glucose handling. In in vivo experiments, we generated muscle-specific miR-16 knockout (KO) mice fed a high-fat diet (HFD) to assess how miR-16 content impacts metabolic and contractile properties including glucose tolerance, insulin sensitivity, muscle contractile function, protein anabolism, and mitochondrial network health. In in vitro experiments, although inhibition of miR-16 induced impaired insulin signaling ( P = 0.002) and glucose uptake ( P = 0.014), overexpression of miR-16 did not attenuate lipid overload-induced insulin resistance using the diacylglycerol analog 1-oleoyl-2-acetyl- sn -glycerol. In in vivo experiments, miR-16 deletion induced both impaired muscle contractility ( P = 0.031-0.033), and mitochondrial network health ( P = 0.008-0.018) in both sexes. However, although males specifically exhibited impaired insulin sensitivity following miR-16 deletion ( P = 0.030), female KO mice showed pronounced glucose intolerance ( P = 0.046), corresponding with lower muscle weights ( P = 0.015), and protein hyperanabolism ( P = 0.023). Our findings suggest distinct sex differences in muscle adaptation in response to miR-16 deletion and miR-16 may serve as a key regulator for metabolic dysregulation in T2DM. NEW & NOTEWORTHY We set to investigate the role of miR-16 in skeletal muscle during diet-induced insulin resistance. Our data provide novel evidence that the lack of miR-16 induced multiple aberrations in insulin sensitivity, muscle contractility, mitochondrial network health, and protein turnover in a sex-dependent manner. Interestingly, miR-16 deletion leads to insulin resistance in males and exacerbated glucose intolerance in females, suggesting different mechanisms of metabolic dysregulation with a lack of miR-16 between sexes.

Cancer cachexia (CC) results in impaired muscle function and quality of life and is the primary cause of death for ∼20%-30% of patients with cancer. We demonstrated mitochondrial degeneration as a precursor to CC in male mice; however, whether such alterations occur in females is currently unknown. The purpose of this study was to elucidate muscle alterations in CC development in female tumor-bearing mice. Sixty female C57BL/6J mice were injected with PBS or Lewis lung carcinoma at 8 wk of age, and tumors developed for 1, 2, 3, or 4 wk to assess the time course of cachectic development. In vivo muscle contractile function, protein fractional synthetic rate (FSR), protein turnover, and mitochondrial health were assessed. Three- and four-week tumor-bearing mice displayed a dichotomy in tumor growth and were reassigned to high tumor (HT) and low tumor (LT) groups. HT mice exhibited lower soleus, tibialis anterior, and fat weights than PBS mice. HT mice showed lower peak isometric torque and slower one-half relaxation time than PBS mice. HT mice had lower FSR than PBS mice, whereas E3 ubiquitin ligases were greater in HT than in other groups. Bnip3 (mitophagy) and pMitoTimer red puncta (mitochondrial degeneration) were greater in HT mice, whereas Pgc1α1 and Tfam (mitochondrial biogenesis) were lower in HT mice than in PBS mice. We demonstrate alterations in female tumor-bearing mice where HT exhibited greater protein degradation, impaired muscle contractility, and mitochondrial degeneration compared with other groups. Our data provide novel evidence for a distinct cachectic development in tumor-bearing female mice compared with previous male studies. NEW & NOTEWORTHY Our study demonstrates divergent tumor development and tissue wasting within 3- and 4-wk mice, where approximately half the mice developed large tumors and subsequent cachexia. Unlike previous male studies, where metabolic perturbations precede the onset of cachexia, females appear to exhibit protections from the metabolic perturbations and cachexia development. Our data provide novel evidence for divergent cachectic development in tumor-bearing female mice compared with previous male CC studies, suggesting different mechanisms of CC between sexes.

Background: Disuse decreases muscle size and is predictive of mortality across multiple pathologies. Detriments to mitochondrial function are hypothesized to underlie disuse-induced muscle atrophy. Little data exist on early mechanisms contributing to onset of these pathologies, nor is it known how they differ between sexes. The purpose of this study was to examine differential and conserved responses to mitochondrial quality control in male and female mice during the development and progression of disuse-induced atrophy., Methods: One hundred C57BL/6J mice (50 male and 50 female) were hindlimb unloaded to induce disuse atrophy for 0 (con), 24, 48, 72, or 168 h. At designated time-points, extensor digitorum longus, gastrocnemius, and soleus muscles were collected for analysis of mitochondrial quality control markers., Results: One hundred sixty-eight hours of disuse resulted in ~25% lower oxidative muscle fibre CSA in both male (P = 0.003) and female (P = 0.02) mice without any differences due to disuse in glycolytic fibres. In male mice, 48 h of unloading was sufficient to result in ~67% greater mitochondrial oxidative stress as assessed by the reporter gene pMitoTimer compared with 0 h (P = 0.002), this mitochondrial stress preceded detectable muscle loss. However in female mice, mitochondrial oxidative stress did not occur until 168 h of disuse (~40% greater mitochondrial oxidative stress in 168 h compared with 0 h of disuse, P < 0.0001). Blunted oxidative stress in female mice appeared to coincide with greater inductions of autophagy and mitophagy in female mice (~3-fold greater BNIP3 and ~6-fold greater LC3II/I ratio P < 0.0001 and P = 0.038 respectively). Male mice overall had greater reactive oxygen species (ROS) production compared with female mice. Female mice had a greater induction of ROS within 24 h of disuse (~4-fold greater compared with 0 h, P < 0.0001); whereas male mice did not have greater ROS production until 168 h of disuse (~2-fold greater, P < 0.0001). Although all muscle types exhibited some alterations to mitochondrial quality control, such as increased markers of mitophagy and fission, the soleus muscle in both male and female mice exhibited consistent alterations to various markers of mitochondrial quality. Markers of mitochondrial translation were approximately 30-50% lower within 24 h of unloading in both male and female soleus muscle (P value ranges: <0.0001-0.03)., Conclusions: Disuse negatively affects mitochondria differentially between sexes during development of muscle wasting. Acutely, female mice may forgo muscle mass to maintain mitochondrial quality compared with male mice. These differences may contribute to divergent clinical manifestations of atrophy., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Young black men who have sex with men (YBMSM) are disproportionately affected by HIV and continue to experience higher rates of new HIV infections when compared to other population groups. As part of the Peer Promotion of Wellness and Enhanced Linkage to Resources Project, we examined problem marijuana use and the overall sexual risk profile of 250 YBMSM. Eighty percent reported prior use of marijuana in their lifetime (n = 200). Among those, problem marijuana use was correlated with problem use of alcohol (r = 0.51, p < 0.001) and other drugs (r = 0.29, p < 0.001); lower household income (r = - .22, p < .01); homelessness (r = 0.15, p < 0.05); incarceration (r = 0.16, p < 0.05); exchanging sex for money, drugs, or shelter (r = 0.18, p < 0.05); having sex with someone known or suspected of having HIV and/or an STI (r = 0.20, p < 0.01); having sex with someone known or suspected of being an injector (r = 0.24, p < 0.01); and having unprotected sex while under the influence of alcohol or drugs (r = 0.32, p < 0.001). The complex relationship between marijuana and sexual risk behavior was examined while accounting for the possible moderating effects of alcohol or other drugs. Problem marijuana, alcohol, and other drug use each made unique contributions to predicting risky sex behavior. A significant marijuana and other drug interaction was found to predict sexual risk behaviors. Future efforts should include holistic intervention approaches for YBMSM that consider factors facilitating high-risk sexual behaviors., (© 2020. W. Montague Cobb-NMA Health Institute.)