A Dyadic Analysis of Criminal Justice Involvement and Sexual HIV Risk Behaviors Among Drug-Involved Men in Community Corrections and Their Intimate Partners in New York City: Implications for Prevention, Treatment and Policies.

People in community corrections have rates of HIV and sexual risk behaviors that are much higher than the general population. Prior literature suggests that criminal justice involvement is associated with increased sexual risk behaviors, yet these studies focus on incarceration and use one-sided study designs that only collect data from one partner. To address gaps in the literature, this study used the Actor Partner-Interdependence Model with Structural Equation Modeling (SEM), to perform a dyadic analysis estimating individual (actor-only) partner-only, and dyadic patterns (actor-partner) of criminal justice involvement and greater sexual risks in a sample of 227 men on probation and their intimate partners in New York City, United States. Standard errors were bootstrapped with 10,000 replications to reduce bias in the significance tests. Goodness of fit indices suggested adequate or better model fit for all the models. Significant actor-only relationships included associations between exposures to arrest, misdemeanor convictions, time spent in jail or prison, felony convictions, lifetime number of incarceration events, prior conviction for disorderly conduct and increased sexual risk behaviors. Partner only effects included significant associations between male partners conviction for a violent crime and their female partners' sexual risk behaviors. Men's encounters with police and number of prior misdemeanors were associated with their own and intimate partners' sexual risk behaviors. Women's prior arrest was associated with their own and intimate partners' sexual risk behaviors. The results from the present study suggest that men on probation and their intimate partners' criminal justice involvement are associated with increased engagement in sexual risk behaviors. It is necessary to conduct greater research into developing dyadic sexual risk reduction and HIV/STI prevention interventions for people who are involved in the criminal justice system.

Assessing the relationship between syringe exchange, pharmacy, and street sources of accessing syringes and injection drug use behavior in a pooled nationally representative sample of people who inject drugs in the United States from 2002 to 2019.

Provision of sterile syringes is an evidence-based strategy of reducing syringe sharing and reusing and yet, access to sterile syringes through pharmacies and syringe exchange programs (SEPs) in the United States remains inadequate. This nationally representative study examined associations between obtaining syringes from pharmacies, SEPs, and sterilizing syringes with bleach and risk of syringe borrowing, lending and reusing syringes in a pooled cross-sectional dataset of 1737 PWID from the 2002-2019 National Survey on Drug Use and Health. Logistic regression was used to produce odds ratios (OR) of the odds of injection drug behaviors after adjusting for obtaining syringes from SEPs, pharmacies, the street, and other sources and potential confounders of race, ethnicity, sex, education, and insurance coverage. Obtaining syringes through SEPs was associated with lower odds of borrowing (OR = .4, CI95% = .2, .9, p = .022) and reusing syringes (OR = .3, CI95% = .2, .6, < .001) compared to obtaining syringes on the street. Obtaining syringes from pharmacies was associated with lower odds of borrowing (OR = .5, CI95% = .3, .9, p = .037) and lending (OR = .5 CI95% = .3, .9, p = .020) syringes. Using bleach to clean syringes was associated with increased odds of borrowing (OR = 2.0, CI95% = 1.3, 3.0, p = .002), lending (OR = 2.0, CI95% = 1.3, 3.0, p = .002) and reusing syringes (OR = 2.4, CI95% = 1.6, 3.6, p < .001). Our findings support provision of syringes through pharmacies and SEPs as a gold-standard strategy of reducing sharing and reuse of syringes in the US.

Cyclin-dependent kinases and cell-cycle transitions: does one fit all?

Cell-cycle transitions in higher eukaryotes are regulated by different cyclin-dependent kinases (CDKs) and their activating cyclin subunits. Based on pioneering findings that a dominant-negative mutation of CDK1 blocks the cell cycle at G2-M phase, whereas dominant-negative CDK2 inhibits the transition into S phase, a model of cell-cycle control has emerged in which each transition is regulated by a specific subset of CDKs and cyclins. Recent work with gene-targeted mice has led to a revision of this model. We discuss cell-cycle control in light of overlapping and essential functions of the different CDKs and cyclins.

HIV testing and access to HIV medical care among people who inject drugs and their intimate partners in Kazakhstan.

BACKGROUND: Growing rates of HIV and high rates of injection drug use in Kazakhstan call for examining access to testing and treatment among people who inject drugs and their intimate partners. OBJECTIVES: We examine how access to health and drug treatment services as well as risk environment factors are associated with ever being tested for HIV and ever receiving any general HIV medical care among 728 male and female intimate partners where at least one partner injects drugs. METHODS: Multivariate random effects logistic regression with random effects for couple were conducted to examine associations between access to health and drug treatment services, risk environment factors, and HIV testing and HIV medical care outcomes. RESULTS: Analyses indicate that accessing needle exchange services and having a regular physician were associated both with access to HIV testing and HIV medical care. Receiving drug treatment was associated with accessing HIV testing but not HIV medical care. Being arrested and charged with a criminal offense was also associated with accessing HIV testing but not HIV medical care. CONCLUSIONS/IMPORTANCE: Study findings highlight the need for increased scale-up of HIV testing efforts, as well as integrated HIV treatment and care in Kazakhstan.

Humpback Dolphins of Western Australia: A Review of Current Knowledge and Recommendations for Future Management.

Among the many cetacean species that occupy Australian coastal waters, Australian humpback dolphins, Sousa sahulensis, are one of the most vulnerable to extirpation due to human activities. This review summarises the existing knowledge, presently occurring and planned research projects, and current conservation measures for humpback dolphins in Western Australia (WA). Rapid and wide-scale coastal development along the northern WA coastline has occurred despite a lack of baseline data for inshore dolphins and, therefore, without a precautionary approach to their conservation. The distribution, abundance, habitat use, and population structure of humpback dolphins remain poorly understood. Less than 1% of their inferred distribution has so far been studied to understand local population demography. The sparse data available suggest that WA humpback dolphins occur as localised populations in low numbers within a range of inshore habitats, including both clear and turbid coastal waters. Marine protected areas cover a third of their inferred distribution in WA, but the efficacy of these reserves in protecting local cetacean populations is unknown. There is a pressing need for coordination and collaboration among scientists, government agencies, industry bodies, Traditional Owners, and local community groups to fill in the gaps of information on humpback dolphins in WA. The recently developed strategies and sampling guidelines developed by state and federal governments should serve as a best practise standard for collection of data aimed at assessing the conservation status of humpback dolphins in WA and Australia.

Sexual Dimorphism and Geographic Variation in Dorsal Fin Features of Australian Humpback Dolphins, Sousa sahulensis.

Determining the sex of free-ranging cetaceans can be challenging. Sexual dimorphism among external features may allow inferences on sex, but such patterns may be difficult to detect and are often confounded by age and geographic variation. Dorsal fin images of 107 female and 54 male Australian humpback dolphins, Sousa sahulensis, from Western Australia (WA) and Queensland (QLD) were used to investigate sex, age and geographic differences in colouration, height/length quotient and number of notches. Adult males exhibited more dorsal fin notches (p<0.001) and a significantly greater loss of pigmentation on the upper half of their dorsal fins (p<0.001) than did adult females. These differences likely reflect that males experience a higher frequency and/or intensity of intraspecific aggression than females. In QLD, heavily spotted dorsal fins were more frequent among females than males (p<0.001). Logistic regression analyses revealed that dorsal fin spotting and loss of pigmentation on the upper half of the dorsal fin provided the best model parameters for predicting the sex of sampled adults, with 97% accuracy. This technique offers a rapid, non-invasive method for predicting sex in Australian humpback dolphins, which could potentially be applied to populations throughout their range. In contrast to adults, presumed immature animals showed little or no loss of pigmentation or spotting; however, the rate of development of these features remains unknown. There were pronounced differences between QLD and WA in the intensity of spotting on dorsal fins and the extent of pigmentation loss around the posterior insertion and trailing edge of the dorsal fin. While based on a limited sample size, these geographic differences may have conservation implications in terms of population subdivision and should be investigated further.

Meiotic inactivation of Xenopus Myt1 by CDK/XRINGO, but not CDK/cyclin, via site-specific phosphorylation.

Cell-cycle progression is regulated by cyclin-dependent kinases (CDKs). CDK1 and CDK2 can be also activated by noncyclin proteins named RINGO/Speedy, which were identified as inducers of the G2/M transition in Xenopus oocytes. However, it is unclear how XRINGO triggers M phase entry in oocytes. We show here that XRINGO-activated CDKs can phosphorylate specific residues in the regulatory domain of Myt1, a Wee1 family kinase that plays a key role in the G2 arrest of oocytes. We have identified three Ser that are major phosphoacceptor sites for CDK/XRINGO but are poorly phosphorylated by CDK/cyclin. Phosphorylation of these Ser inhibits Myt1 activity, whereas their mutation makes Myt1 resistant to inhibition by CDK/XRINGO. Our results demonstrate that XRINGO-activated CDKs have different substrate specificity than the CDK/cyclin complexes. We also describe a mechanism of Myt1 regulation based on site-specific phosphorylation, which is likely to mediate the induction of G2/M transition in oocytes by XRINGO.

Pursuing the impossible: an interview with Tim Hunt.

Tim Hunt took an undergraduate degree in Natural Sciences at Cambridge in 1964, and his PhD and subsequent work focussed on the control of protein synthesis until 1982, when his adventitious discovery of the central cell cycle regulator cyclin, while he was teaching at the Marine Biological Laboratory in Woods Hole, redirected him to the study of cell cycle regulation. From 1990 to his retirement Tim worked in the Clare Hall Laboratories of Cancer Research UK. He shared the Nobel Prize in Physiology and Medicine with Lee Hartwell and Paul Nurse in 2001, and talked to us about the series of coincidences that led him to the prizewinning discovery.

Depression Among People Who Inject Drugs and Their Intimate Partners in Kazakhstan.

This paper examines individual, social, and structural factors associated with depression among 728 people who inject drugs (PWID) and their intimate partners in Kazakhstan, with separate multivariate models by gender. Depression scores were higher on average among participants of both genders who recently experienced sexual intimate partner violence, food insecurity, and who had lower levels of self-rated health. Among females, higher depression scores were associated with experiencing childhood sexual abuse, lower levels of social support, and not having children. Findings highlight a need to incorporate gender differences and factors associated with depression in designing mental health services for PWID in Kazakhstan.

Protein phosphatases and their regulation in the control of mitosis.

Cell cycle transitions depend on protein phosphorylation and dephosphorylation. The discovery of cyclin-dependent kinases (CDKs) and their mode of activation by their cyclin partners explained many important aspects of cell cycle control. As the cell cycle is basically a series of recurrences of a defined set of events, protein phosphatases must obviously be as important as kinases. However, our knowledge about phosphatases lags well behind that of kinases. We still do not know which phosphatase(s) is/are truly responsible for dephosphorylating CDK substrates, and we know very little about whether and how protein phosphatases are regulated. Here, we summarize our present understanding of the phosphatases that are important in the control of the cell cycle and pose the questions that need to be answered as regards the regulation of protein phosphatases.

An Approach to Enhancing Medication Treatment for Opioid Use Disorder in the HEALing Communities Study.

The HEALing (Helping to End Addiction Long-term) Communities Study (HCS) aims to test the effectiveness of the Communities That HEAL intervention in decreasing opioid overdose deaths in 67 communities across four U.S. states. This intervention enlists a collaborative team of researchers, academic experts, and community coalitions to select and implement interventions from a menu of evidence-based practices, including medications for opioid use disorder (MOUD). The HCS's New York team developed an integrated network systems (INS) approach with a mapping tool to coach coalitions in the selection of strategies to enhance medication treatment. With the INS approach, community coalitions develop a map of service delivery venues in their local county to better engage people with medication treatment wherever this need arises. The map is structured around core services that can provide maintenance MOUD and satellite services, which include all settings where people with opioid use disorder are encountered and can be identified, possibly given medication, and referred to core programs for ongoing MOUD care. This article describes the rationale for the INS mapping tool, with a discussion framed by the consolidated framework for implementation research, and provides a case example of its application.

Regulated activity of PP2A-B55 delta is crucial for controlling entry into and exit from mitosis in Xenopus egg extracts.

Entry into mitosis depends on the activity of cyclin-dependent kinases (CDKs). Conversely, exit from mitosis occurs when mitotic cyclins are degraded, thereby extinguishing CDK activity. Exit from mitosis must also require mitotic phosphoproteins to revert to their interphase hypophosphorylated forms, but there is a controversy about which phosphatase(s) is/are responsible for dephosphorylating the CDK substrates. We find that PP2A associated with a B55 delta subunit is relatively specific for a model mitotic CDK substrate in Xenopus egg extracts. The phosphatase activity measured by this substrate is regulated during the cell cycle--high in interphase and suppressed during mitosis. Depletion of PP2A-B55 delta (in interphase) from 'cycling' frog egg extracts accelerated their entry into mitosis and kept them indefinitely in mitosis. When PP2A-B55 delta was depleted from mitotic extracts, however, exit from mitosis was hardly delayed, showing that other phosphatase(s) are also required for mitotic exit. Increasing the concentration of PP2A-B55 delta in extracts by adding recombinant enzyme inhibited the entry into mitosis. This form of PP2A seems to be a key regulator of entry into and exit from mitosis.

Tipin/Tim1/And1 protein complex promotes Pol alpha chromatin binding and sister chromatid cohesion.

The Tipin/Tim1 complex plays an important role in the S-phase checkpoint and replication fork stability. However, the biochemical function of this complex is poorly understood. Using Xenopus laevis egg extract we show that Tipin is required for DNA replication in the presence of limiting amount of replication origins. Under these conditions the DNA replication defect correlates with decreased levels of DNA Polalpha on chromatin. We identified And1, a Polalpha chromatin-loading factor, as new Tipin-binding partner. We found that both Tipin and And1 promote stable binding of Polalpha to chromatin and that this is required for DNA replication under unchallenged conditions. Strikingly, extracts lacking Tipin and And1 also show reduced sister chromatids cohesion. These data indicate that Tipin/Tim1/And1 form a complex that links stabilization of replication fork and establishment of sister chromatid cohesion.

HIV among injection drug users and their intimate partners in Almaty, Kazakhstan.

This paper examines prevalence rates of HIV, HCV, and syphilis among a sample of injecting drug users (IDUs) and their heterosexual intimate partners (N = 728) from Almaty, Kazakhstan. The study uses baseline data from Project Renaissance, a couple-based HIV prevention intervention delivered to a couple where one or both partners are IDUs. HIV prevalence rates among female and male IDUs were 28 %. Among the full sample, 75 % had HCV, and 13 % tested positive for the syphilis antibody test. Only 10 % of the sample ever visited a needle exchange program. One-fourth (25.3 %) had never been tested for HIV. One-quarter of those who tested positive were unaware of their status. Being HIV positive was associated with a history of incarceration, being an IDU, and having access to needle exchange programs. The findings call for increasing efforts to improve access to HIV testing, prevention, treatment, and care for IDUs in Almaty, Kazakhstan.

Calcineurin is required to release Xenopus egg extracts from meiotic M phase.

Fertilization induces a transient increase in cytoplasmic Ca2+ concentration in animal eggs that releases them from cell cycle arrest in the second meiotic metaphase. In frog eggs, Ca2+ activates Ca2+/calmodulin-activated kinase, which inactivates cytostatic factor, allowing the anaphase-promoting factor to turn on and ubiquitinate cyclins and securin, which returns the cell cycle to interphase. Here we show that the calcium-activated protein phosphatase calcineurin is also important in this process. Calcineurin is transiently activated after adding Ca2+ to egg extracts, and inhibitors of calcineurin such as cyclosporin A (ref. 8) delay the destruction of cyclins, the global dephosphorylation of M-phase-specific phosphoproteins and the re-formation of a fully functional nuclear envelope. We found that a second wave of phosphatase activity directed at mitotic phosphoproteins appears after the spike of calcineurin activity. This activity disappeared the next time the extract entered M phase and reappeared at the end of mitosis. We surmise that inhibition of this second phosphatase activity is important in allowing cells to enter mitosis, and, conversely, that its activation is required for a timely return to interphase. Calcineurin is required to break the deep cell cycle arrest imposed by the Mos-MAP (mitogen-activated protein) kinase pathway, and we show that Fizzy/Cdc20, a key regulator of the anaphase-promoting factor, is an excellent substrate for this phosphatase.

The policy landscape for naloxone distribution in four states highly impacted by fatal opioid overdoses.

Background: Expanding access to naloxone is one of the most impactful interventions in decreasing opioid-related mortality. However, state distribution rates of naloxone are insufficient to meet community need. The current study sought to better understand this gap by focusing on state policies that may facilitate or impede naloxone distribution in four states highly impacted by fatal opioid overdoses - Kentucky, Massachusetts, New York, and Ohio. Methods: We provide a descriptive analysis of the policy landscape impacting naloxone distribution through pharmacy and community channels in the four states participating in the HEALing Communities Study (HCS). Publicly available data and the expertise of the research team were used to describe each state's naloxone access laws (NALs), Medicaid coverage of naloxone, and community overdose education and naloxone distribution infrastructure. Data presented in this study represent the most current policy landscape through September 2022. Results: Variation exists between specific components of the NALs of each state, the structure of Medicaid coverage of naloxone, and the community distribution infrastructure networks. Massachusetts and New York have a statewide standing order, but other states use different strategies short of a statewide standing order to expand access to naloxone. Quantity limits specific to naloxone may limit access to Medicaid beneficiaries in some states. Conclusion: States participating in the HCS have developed innovative but different mechanisms to ensure naloxone access. Policies were dynamic and moved towards greater access. Research should consider the policy landscape in the implementation and sustainability of interventions as well as the analysis of outcomes.

An essential role for Cdk1 in S phase control is revealed via chemical genetics in vertebrate cells.

In vertebrates Cdk1 is required to initiate mitosis; however, any functionality of this kinase during S phase remains unclear. To investigate this, we generated chicken DT40 mutants, in which an analog-sensitive mutant cdk1 as replaces the endogenous Cdk1, allowing us to specifically inactivate Cdk1 using bulky ATP analogs. In cells that also lack Cdk2, we find that Cdk1 activity is essential for DNA replication initiation and centrosome duplication. The presence of a single Cdk2 allele renders S phase progression independent of Cdk1, which suggests a complete overlap of these kinases in S phase control. Moreover, we find that Cdk1 inhibition did not induce re-licensing of replication origins in G2 phase. Conversely, inhibition during mitosis of Cdk1 causes rapid activation of endoreplication, depending on proteolysis of the licensing inhibitor Geminin. This study demonstrates essential functions of Cdk1 in the control of S phase, and exemplifies a chemical genetics approach to target cyclin-dependent kinases in vertebrate cells.

Loss of the mammalian APC/C activator FZR1 shortens G1 and lengthens S phase but has little effect on exit from mitosis.

The anaphase-promoting complex/cyclosome (APC/C) is essential for progression through mitosis. At anaphase onset, the APC/C requires the activator protein CDC20 to target securin and cyclin B1 for proteasome-dependent degradation, but then depends on the CDC20-related protein FZR1 (also known as CDH1) to remain active until the onset of the next S phase. To investigate the role of FZR1 in mammalian cells, we used RNAi in human cell lines and conditional gene targeting in mouse embryonic fibroblasts. In neither case was FZR1 required for exit from mitosis, but in cells lacking FZR1, the G1 phase was shortened and the S phase was prolonged. In several normal and transformed human cell lines, loss of FZR1 function induced DNA-damage responses and impaired proliferation independently of the p53 status. Constitutive knockdown of p53 in U2OS cells with inducible FZR1 siRNA also failed to restore their proliferative capacity. Thus, the proliferation defects are a direct consequence of the genetic damage inflicted by loss of FZR1 function and are largely independent of p53. In summary, mammalian FZR1 is not required for the completion of mitosis, but is an important regulator of G1 phase and is required for efficient DNA replication in human and mouse somatic cells.

CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair.

Inherited mutations in BRCA2 are associated with a predisposition to early-onset breast cancers. The underlying basis of tumorigenesis is thought to be linked to defects in DNA double-strand break repair by homologous recombination. Here we show that the carboxy-terminal region of BRCA2, which interacts directly with the essential recombination protein RAD51, contains a site (serine 3291; S3291) that is phosphorylated by cyclin-dependent kinases. Phosphorylation of S3291 is low in S phase when recombination is active, but increases as cells progress towards mitosis. This modification blocks C-terminal interactions between BRCA2 and RAD51. However, DNA damage overcomes cell cycle regulation by decreasing S3291 phosphorylation and stimulating interactions with RAD51. These results indicate that S3291 phosphorylation might provide a molecular switch to regulate RAD51 recombination activity, providing new insight into why BRCA2 C-terminal deletions lead to radiation sensitivity and cancer predisposition.